--- _id: '14794' abstract: - lang: eng text: "Mosaic analysis with double markers (MADM) technology enables the sparse labeling of genetically defined neurons. We present a protocol for time-lapse imaging of cortical projection neuron migration in mice using MADM. We describe steps for the isolation, culturing, and 4D imaging of neuronal dynamics in MADM-labeled brain tissue. While this protocol is compatible with other single-cell labeling methods, the MADM approach provides a genetic platform for the functional assessment of cell-autonomous candidate gene function and the relative contribution of non-cell-autonomous effects.\r\n\r\nFor complete details on the use and execution of this protocol, please refer to Hansen et al. (2022),1 Contreras et al. (2021),2 and Amberg and Hippenmeyer (2021).3" acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: We thank Florian Pauler for discussion and his expert technical support. This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging and Optics Facility (IOF) and Preclinical Facility (PCF). A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. article_number: '102795' article_processing_charge: Yes article_type: review author: - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Hansen AH, Hippenmeyer S. Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. STAR Protocols. 2024;5(1). doi:10.1016/j.xpro.2023.102795 apa: Hansen, A. H., & Hippenmeyer, S. (2024). Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2023.102795 chicago: Hansen, Andi H, and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols. Elsevier, 2024. https://doi.org/10.1016/j.xpro.2023.102795. ieee: A. H. Hansen and S. Hippenmeyer, “Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers,” STAR Protocols, vol. 5, no. 1. Elsevier, 2024. ista: Hansen AH, Hippenmeyer S. 2024. Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. STAR Protocols. 5(1), 102795. mla: Hansen, Andi H., and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols, vol. 5, no. 1, 102795, Elsevier, 2024, doi:10.1016/j.xpro.2023.102795. short: A.H. Hansen, S. Hippenmeyer, STAR Protocols 5 (2024). date_created: 2024-01-14T23:00:56Z date_published: 2024-01-01T00:00:00Z date_updated: 2024-01-17T10:32:31Z day: '01' department: - _id: SiHi doi: 10.1016/j.xpro.2023.102795 external_id: pmid: - '38165800' intvolume: ' 5' issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.xpro.2023.102795 month: '01' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration publication: STAR Protocols publication_identifier: eissn: - 2666-1667 publication_status: epub_ahead publisher: Elsevier quality_controlled: '1' related_material: link: - relation: software url: http://github.com/hippenmeyerlab scopus_import: '1' status: public title: Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 5 year: '2024' ... --- _id: '12875' abstract: - lang: eng text: The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and is composed of a rich diversity of excitatory and inhibitory neurons and glia. However, the developmental principles directing the generation of SC cell-type diversity are not understood. Here, we pursued systematic cell lineage tracing in silico and in vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal analysis with single-cell sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron types, even at the stage of terminal division. While individual clonal units show no pre-defined cellular composition, the establishment of appropriate relative proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively, our findings provide an inaugural framework at the single-RGP/-cell level of the mammalian SC ontogeny. acknowledged_ssus: - _id: Bio - _id: M-Shop - _id: LifeSc - _id: PreCl acknowledgement: "We thank Liqun Luo for his continued support, for providing essential resources for generating Fzd10-CreER mice which were generated in his laboratory, and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic mouse line for this study; A. Heger for mouse colony management; R. Beattie and T. Asenov for designing and producing components of acute slice recovery chamber for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial experiments, technical support and/or assistance. This study was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds; the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H. " article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Giselle T full_name: Cheung, Giselle T id: 471195F6-F248-11E8-B48F-1D18A9856A87 last_name: Cheung orcid: 0000-0001-8457-2572 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Thomas full_name: Krausgruber, Thomas last_name: Krausgruber - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Martin full_name: Schrammel, Martin id: f13e7cae-e8bd-11ed-841a-96dedf69f46d last_name: Schrammel - first_name: Natalie Y full_name: Özgen, Natalie Y id: e68ece33-f6e0-11ea-865d-ae1031dcc090 last_name: Özgen - first_name: Alexis full_name: Ivec, Alexis id: 1d144691-e8be-11ed-9b33-bdd3077fad4c last_name: Ivec - first_name: Christoph full_name: Bock, Christoph last_name: Bock - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Cheung GT, Pauler F, Koppensteiner P, et al. Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. 2024;112(2):230-246.e11. doi:10.1016/j.neuron.2023.11.009 apa: Cheung, G. T., Pauler, F., Koppensteiner, P., Krausgruber, T., Streicher, C., Schrammel, M., … Hippenmeyer, S. (2024). Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.11.009 chicago: Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, Thomas Krausgruber, Carmen Streicher, Martin Schrammel, Natalie Y Özgen, et al. “Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus.” Neuron. Elsevier, 2024. https://doi.org/10.1016/j.neuron.2023.11.009. ieee: G. T. Cheung et al., “Multipotent progenitors instruct ontogeny of the superior colliculus,” Neuron, vol. 112, no. 2. Elsevier, p. 230–246.e11, 2024. ista: Cheung GT, Pauler F, Koppensteiner P, Krausgruber T, Streicher C, Schrammel M, Özgen NY, Ivec A, Bock C, Shigemoto R, Hippenmeyer S. 2024. Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. 112(2), 230–246.e11. mla: Cheung, Giselle T., et al. “Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus.” Neuron, vol. 112, no. 2, Elsevier, 2024, p. 230–246.e11, doi:10.1016/j.neuron.2023.11.009. short: G.T. Cheung, F. Pauler, P. Koppensteiner, T. Krausgruber, C. Streicher, M. Schrammel, N.Y. Özgen, A. Ivec, C. Bock, R. Shigemoto, S. Hippenmeyer, Neuron 112 (2024) 230–246.e11. date_created: 2023-04-27T09:41:48Z date_published: 2024-01-17T00:00:00Z date_updated: 2024-03-05T09:43:02Z day: '17' ddc: - '570' department: - _id: SiHi - _id: RySh doi: 10.1016/j.neuron.2023.11.009 external_id: pmid: - '38096816' file: - access_level: open_access checksum: 32b3788f7085cf44a84108d8faaff3ce content_type: application/pdf creator: dernst date_created: 2024-02-06T13:56:15Z date_updated: 2024-02-06T13:56:15Z file_id: '14944' file_name: 2024_Neuron_Cheung.pdf file_size: 5942467 relation: main_file success: 1 file_date_updated: 2024-02-06T13:56:15Z has_accepted_license: '1' intvolume: ' 112' issue: '2' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '01' oa: 1 oa_version: Published Version page: 230-246.e11 pmid: 1 project: - _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E grant_number: F07805 name: Molecular Mechanisms of Neural Stem Cell Lineage Progression publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/the-pedigree-of-brain-cells/ scopus_import: '1' status: public title: Multipotent progenitors instruct ontogeny of the superior colliculus tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 112 year: '2024' ... --- _id: '12542' abstract: - lang: eng text: In this issue of Neuron, Espinosa-Medina et al.1 present the TEMPO (Temporal Encoding and Manipulation in a Predefined Order) system, which enables the marking and genetic manipulation of sequentially generated cell lineages in vertebrate species in vivo. article_processing_charge: No article_type: letter_note author: - first_name: Ana full_name: Villalba Requena, Ana id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247 last_name: Villalba Requena orcid: 0000-0002-5615-5277 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Villalba Requena A, Hippenmeyer S. Going back in time with TEMPO. Neuron. 2023;111(3):291-293. doi:10.1016/j.neuron.2023.01.006 apa: Villalba Requena, A., & Hippenmeyer, S. (2023). Going back in time with TEMPO. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.01.006 chicago: Villalba Requena, Ana, and Simon Hippenmeyer. “Going Back in Time with TEMPO.” Neuron. Elsevier, 2023. https://doi.org/10.1016/j.neuron.2023.01.006. ieee: A. Villalba Requena and S. Hippenmeyer, “Going back in time with TEMPO,” Neuron, vol. 111, no. 3. Elsevier, pp. 291–293, 2023. ista: Villalba Requena A, Hippenmeyer S. 2023. Going back in time with TEMPO. Neuron. 111(3), 291–293. mla: Villalba Requena, Ana, and Simon Hippenmeyer. “Going Back in Time with TEMPO.” Neuron, vol. 111, no. 3, Elsevier, 2023, pp. 291–93, doi:10.1016/j.neuron.2023.01.006. short: A. Villalba Requena, S. Hippenmeyer, Neuron 111 (2023) 291–293. date_created: 2023-02-12T23:00:58Z date_published: 2023-02-01T00:00:00Z date_updated: 2023-08-01T13:10:27Z day: '01' department: - _id: SiHi doi: 10.1016/j.neuron.2023.01.006 external_id: isi: - '000994473300001' intvolume: ' 111' isi: 1 issue: '3' language: - iso: eng month: '02' oa_version: None page: 291-293 publication: Neuron publication_identifier: eissn: - 1097-4199 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Going back in time with TEMPO type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 111 year: '2023' ... --- _id: '12679' abstract: - lang: eng text: How to generate a brain of correct size and with appropriate cell-type diversity during development is a major question in Neuroscience. In the developing neocortex, radial glial progenitor (RGP) cells are the main neural stem cells that produce cortical excitatory projection neurons, glial cells, and establish the prospective postnatal stem cell niche in the lateral ventricles. RGPs follow a tightly orchestrated developmental program that when disrupted can result in severe cortical malformations such as microcephaly and megalencephaly. The precise cellular and molecular mechanisms instructing faithful RGP lineage progression are however not well understood. This review will summarize recent conceptual advances that contribute to our understanding of the general principles of RGP lineage progression. acknowledgement: "I wish to thank all current and past members of the Hippenmeyer laboratory at ISTA for exciting discussions on the subject of this review. I apologize to colleagues whose work I could not cite and/or discuss in the frame of the available space. Work in the Hippenmeyer laboratory on the\r\ndiscussed topic is supported by ISTA institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agree-ment no. 725780 LinPro) to SH." article_number: '102695' article_processing_charge: Yes (via OA deal) article_type: review author: - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: 'Hippenmeyer S. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. Current Opinion in Neurobiology. 2023;79(4). doi:10.1016/j.conb.2023.102695' apa: 'Hippenmeyer, S. (2023). Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. Current Opinion in Neurobiology. Elsevier. https://doi.org/10.1016/j.conb.2023.102695' chicago: 'Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights from Developing Cerebral Cortex.” Current Opinion in Neurobiology. Elsevier, 2023. https://doi.org/10.1016/j.conb.2023.102695.' ieee: 'S. Hippenmeyer, “Principles of neural stem cell lineage progression: Insights from developing cerebral cortex,” Current Opinion in Neurobiology, vol. 79, no. 4. Elsevier, 2023.' ista: 'Hippenmeyer S. 2023. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. Current Opinion in Neurobiology. 79(4), 102695.' mla: 'Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights from Developing Cerebral Cortex.” Current Opinion in Neurobiology, vol. 79, no. 4, 102695, Elsevier, 2023, doi:10.1016/j.conb.2023.102695.' short: S. Hippenmeyer, Current Opinion in Neurobiology 79 (2023). date_created: 2023-02-26T12:24:21Z date_published: 2023-04-01T00:00:00Z date_updated: 2023-08-16T12:30:25Z day: '01' ddc: - '570' department: - _id: SiHi doi: 10.1016/j.conb.2023.102695 ec_funded: 1 external_id: isi: - '000953497700001' pmid: - '36842274' file: - access_level: open_access checksum: 4d11c4ca87e6cbc4d2ac46d3225ea615 content_type: application/pdf creator: dernst date_created: 2023-08-16T12:29:06Z date_updated: 2023-08-16T12:29:06Z file_id: '14071' file_name: 2023_CurrentOpinionNeurobio_Hippenmeyer.pdf file_size: 1787894 relation: main_file success: 1 file_date_updated: 2023-08-16T12:29:06Z has_accepted_license: '1' intvolume: ' 79' isi: 1 issue: '4' keyword: - General Neuroscience language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E grant_number: F07805 name: Molecular Mechanisms of Neural Stem Cell Lineage Progression - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: Current Opinion in Neurobiology publication_identifier: issn: - 0959-4388 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'Principles of neural stem cell lineage progression: Insights from developing cerebral cortex' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 79 year: '2023' ... --- _id: '12562' abstract: - lang: eng text: Presynaptic inputs determine the pattern of activation of postsynaptic neurons in a neural circuit. Molecular and genetic pathways that regulate the selective formation of subsets of presynaptic inputs are largely unknown, despite significant understanding of the general process of synaptogenesis. In this study, we have begun to identify such factors using the spinal monosynaptic stretch reflex circuit as a model system. In this neuronal circuit, Ia proprioceptive afferents establish monosynaptic connections with spinal motor neurons that project to the same muscle (termed homonymous connections) or muscles with related or synergistic function. However, monosynaptic connections are not formed with motor neurons innervating muscles with antagonistic functions. The ETS transcription factor ER81 (also known as ETV1) is expressed by all proprioceptive afferents, but only a small set of motor neuron pools in the lumbar spinal cord of the mouse. Here we use conditional mouse genetic techniques to eliminate Er81 expression selectively from motor neurons. We find that ablation of Er81 in motor neurons reduces synaptic inputs from proprioceptive afferents conveying information from homonymous and synergistic muscles, with no change observed in the connectivity pattern from antagonistic proprioceptive afferents. In summary, these findings suggest a role for ER81 in defined motor neuron pools to control the assembly of specific presynaptic inputs and thereby influence the profile of activation of these motor neurons. acknowledgement: The authors gratefully thank Dr. Silvia Arber, University of Basel and Friedrich Miescher Institute for Biomedical Research, for support and in whose lab the data were collected. For advice on statistical analysis, we thank Michael Bottomley from the Statistical Consulting Center, College of Science and Mathematics, Wright State University. article_processing_charge: No article_type: original author: - first_name: David R. full_name: Ladle, David R. last_name: Ladle - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Ladle DR, Hippenmeyer S. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology. 2023;129(3):501-512. doi:10.1152/jn.00172.2022 apa: Ladle, D. R., & Hippenmeyer, S. (2023). Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology. American Physiological Society. https://doi.org/10.1152/jn.00172.2022 chicago: Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” Journal of Neurophysiology. American Physiological Society, 2023. https://doi.org/10.1152/jn.00172.2022. ieee: D. R. Ladle and S. Hippenmeyer, “Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons,” Journal of Neurophysiology, vol. 129, no. 3. American Physiological Society, pp. 501–512, 2023. ista: Ladle DR, Hippenmeyer S. 2023. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology. 129(3), 501–512. mla: Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” Journal of Neurophysiology, vol. 129, no. 3, American Physiological Society, 2023, pp. 501–12, doi:10.1152/jn.00172.2022. short: D.R. Ladle, S. Hippenmeyer, Journal of Neurophysiology 129 (2023) 501–512. date_created: 2023-02-15T14:46:14Z date_published: 2023-03-01T00:00:00Z date_updated: 2023-09-05T12:13:34Z day: '01' department: - _id: SiHi doi: 10.1152/jn.00172.2022 external_id: isi: - '000957721600001' pmid: - '36695533' intvolume: ' 129' isi: 1 issue: '3' keyword: - Physiology - General Neuroscience language: - iso: eng month: '03' oa_version: None page: 501-512 pmid: 1 publication: Journal of Neurophysiology publication_identifier: eissn: - 1522-1598 issn: - 0022-3077 publication_status: published publisher: American Physiological Society quality_controlled: '1' status: public title: Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 129 year: '2023' ... --- _id: '14647' abstract: - lang: eng text: In the developing vertebrate central nervous system, neurons and glia typically arise sequentially from common progenitors. Here, we report that the transcription factor Forkhead Box G1 (Foxg1) regulates gliogenesis in the mouse neocortex via distinct cell-autonomous roles in progenitors and in postmitotic neurons that regulate different aspects of the gliogenic FGF signalling pathway. We demonstrate that loss of Foxg1 in cortical progenitors at neurogenic stages causes premature astrogliogenesis. We identify a novel FOXG1 target, the pro-gliogenic FGF pathway component Fgfr3, which is suppressed by FOXG1 cell-autonomously to maintain neurogenesis. Furthermore, FOXG1 can also suppress premature astrogliogenesis triggered by the augmentation of FGF signalling. We identify a second novel function of FOXG1 in regulating the expression of gliogenic ligand FGF18 in new born neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons increases Fgf18 expression and enhances gliogenesis in the progenitors. These results fit well with the model that new born neurons secrete cues that trigger progenitors to produce the next wave of cell types, astrocytes. If FGF signalling is attenuated in Foxg1 null progenitors, they progress to oligodendrocyte production. Therefore, loss of FOXG1 transitions the progenitor to a gliogenic state, producing either astrocytes or oligodendrocytes depending on FGF signalling levels. Our results uncover how FOXG1 integrates extrinsic signalling via the FGF pathway to regulate the sequential generation of neurons, astrocytes, and oligodendrocytes in the cerebral cortex. acknowledgement: "We thank Dr. Shital Suryavanshi and the animal house staff of the Tata Institute of\r\nFundamental Research (TIFR) for their excellent support; Gord Fishell and Goichi Miyoshi for\r\nthe Foxg1 floxed mouse line; Hiroshi Kawasaki for the plasmids pCAG-FGF8 and pCAGsFGFR3c. We thank Prof. S.K. Lee for the Foxg1lox/lox genotyping primers and protocol. We thank Dr. Deepak Modi and Dr. Vainav Patel for allowing us to use the NIRRCH FACS Facility and the staff of the NIRRCH and TIFR FACS facilities for their assistance.\r\nWe thank Denis Jabaudon for his critical comments on the manuscript and members of the\r\nJabaudon lab for helpful discussions. This work was funded by the Department of Atomic\r\nEnergy (DAE), Govt. of India (Project Identification no. RTI4003, DAE OM no.\r\n1303/2/2019/R&D-II/DAE/2079)." article_processing_charge: No author: - first_name: Mahima full_name: Bose, Mahima last_name: Bose - first_name: Varun full_name: Suresh, Varun last_name: Suresh - first_name: Urvi full_name: Mishra, Urvi last_name: Mishra - first_name: Ishita full_name: Talwar, Ishita last_name: Talwar - first_name: Anuradha full_name: Yadav, Anuradha last_name: Yadav - first_name: Shiona full_name: Biswas, Shiona last_name: Biswas - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Shubha full_name: Tole, Shubha last_name: Tole citation: ama: Bose M, Suresh V, Mishra U, et al. Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. bioRxiv. doi:10.1101/2023.11.30.569337 apa: Bose, M., Suresh, V., Mishra, U., Talwar, I., Yadav, A., Biswas, S., … Tole, S. (n.d.). Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2023.11.30.569337 chicago: Bose, Mahima, Varun Suresh, Urvi Mishra, Ishita Talwar, Anuradha Yadav, Shiona Biswas, Simon Hippenmeyer, and Shubha Tole. “Dual Role of FOXG1 in Regulating Gliogenesis in the Developing Neocortex via the FGF Signalling Pathway.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2023.11.30.569337. ieee: M. Bose et al., “Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway,” bioRxiv. Cold Spring Harbor Laboratory. ista: Bose M, Suresh V, Mishra U, Talwar I, Yadav A, Biswas S, Hippenmeyer S, Tole S. Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. bioRxiv, 10.1101/2023.11.30.569337. mla: Bose, Mahima, et al. “Dual Role of FOXG1 in Regulating Gliogenesis in the Developing Neocortex via the FGF Signalling Pathway.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2023.11.30.569337. short: M. Bose, V. Suresh, U. Mishra, I. Talwar, A. Yadav, S. Biswas, S. Hippenmeyer, S. Tole, BioRxiv (n.d.). date_created: 2023-12-06T13:07:01Z date_published: 2023-12-01T00:00:00Z date_updated: 2023-12-11T07:37:17Z day: '01' department: - _id: SiHi doi: 10.1101/2023.11.30.569337 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2023.11.30.569337 month: '12' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory status: public title: Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '14683' abstract: - lang: eng text: "Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.\r\nFor complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1" acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging & Optics Facility (IOF) and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme (T 1031). G.C. received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411 as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H. article_number: '102771' article_processing_charge: No article_type: review author: - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Giselle T full_name: Cheung, Giselle T id: 471195F6-F248-11E8-B48F-1D18A9856A87 last_name: Cheung orcid: 0000-0001-8457-2572 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 2023;5(1). doi:10.1016/j.xpro.2023.102771 apa: Amberg, N., Cheung, G. T., & Hippenmeyer, S. (2023). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2023.102771 chicago: Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” STAR Protocols. Elsevier, 2023. https://doi.org/10.1016/j.xpro.2023.102771. ieee: N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry,” STAR Protocols, vol. 5, no. 1. Elsevier, 2023. ista: Amberg N, Cheung GT, Hippenmeyer S. 2023. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 5(1), 102771. mla: Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” STAR Protocols, vol. 5, no. 1, 102771, Elsevier, 2023, doi:10.1016/j.xpro.2023.102771. short: N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2023). date_created: 2023-12-13T11:48:05Z date_published: 2023-12-08T00:00:00Z date_updated: 2023-12-18T08:06:14Z day: '08' ddc: - '570' department: - _id: SiHi doi: 10.1016/j.xpro.2023.102771 ec_funded: 1 external_id: pmid: - '38070137' intvolume: ' 5' issue: '1' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Neuroscience language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.xpro.2023.102771 month: '12' oa: 1 oa_version: Submitted Version pmid: 1 project: - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E grant_number: F07805 name: Molecular Mechanisms of Neural Stem Cell Lineage Progression - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: STAR Protocols publication_identifier: issn: - 2666-1667 publication_status: epub_ahead publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 5 year: '2023' ... --- _id: '14757' abstract: - lang: eng text: The cerebral cortex is comprised of a vast cell-type diversity sequentially generated by cortical progenitor cells. Faithful progenitor lineage progression requires the tight orchestration of distinct molecular and cellular mechanisms regulating proper progenitor proliferation behavior and differentiation. Correct execution of developmental programs involves a complex interplay of cell intrinsic and tissue-wide mechanisms. Many studies over the past decades have been able to determine a plethora of genes critically involved in cortical development. However, only a few made use of genetic paradigms with sparse and global gene deletion to probe cell-autonomous vs. tissue-wide contribution. In this chapter, we will elaborate on the importance of dissecting the cell-autonomous and tissue-wide mechanisms to gain a precise understanding of gene function during radial glial progenitor lineage progression. article_processing_charge: No author: - first_name: Ana full_name: Villalba Requena, Ana id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247 last_name: Villalba Requena orcid: 0000-0002-5615-5277 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: 'Villalba Requena A, Amberg N, Hippenmeyer S. Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression. In: Huttner W, ed. Neocortical Neurogenesis in Development and Evolution. Wiley; 2023:169-191. doi:10.1002/9781119860914.ch10' apa: Villalba Requena, A., Amberg, N., & Hippenmeyer, S. (2023). Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression. In W. Huttner (Ed.), Neocortical Neurogenesis in Development and Evolution (pp. 169–191). Wiley. https://doi.org/10.1002/9781119860914.ch10 chicago: Villalba Requena, Ana, Nicole Amberg, and Simon Hippenmeyer. “Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression.” In Neocortical Neurogenesis in Development and Evolution, edited by Wieland Huttner, 169–91. Wiley, 2023. https://doi.org/10.1002/9781119860914.ch10. ieee: A. Villalba Requena, N. Amberg, and S. Hippenmeyer, “Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression,” in Neocortical Neurogenesis in Development and Evolution, W. Huttner, Ed. Wiley, 2023, pp. 169–191. ista: 'Villalba Requena A, Amberg N, Hippenmeyer S. 2023.Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression. In: Neocortical Neurogenesis in Development and Evolution. , 169–191.' mla: Villalba Requena, Ana, et al. “Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression.” Neocortical Neurogenesis in Development and Evolution, edited by Wieland Huttner, Wiley, 2023, pp. 169–91, doi:10.1002/9781119860914.ch10. short: A. Villalba Requena, N. Amberg, S. Hippenmeyer, in:, W. Huttner (Ed.), Neocortical Neurogenesis in Development and Evolution, Wiley, 2023, pp. 169–191. date_created: 2024-01-08T13:16:36Z date_published: 2023-08-08T00:00:00Z date_updated: 2024-01-09T09:46:57Z day: '08' department: - _id: SiHi doi: 10.1002/9781119860914.ch10 editor: - first_name: Wieland full_name: Huttner, Wieland last_name: Huttner language: - iso: eng month: '08' oa_version: None page: 169-191 publication: Neocortical Neurogenesis in Development and Evolution publication_identifier: eisbn: - '9781119860914' publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '14783' abstract: - lang: eng text: Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic astroglial processes and plays major roles in synaptic transmission. We have previously found that astroglial Cx43 controls synaptic glutamate levels and allows for activity-dependent glutamine release to sustain physiological synaptic transmissions and cognitiogns. However, whether Cx43 is important for the release of synaptic vesicles, which is a critical component of synaptic efficacy, remains unanswered. Here, using transgenic mice with a glial conditional knockout of Cx43 (Cx43−/−), we investigate whether and how astrocytes regulate the release of synaptic vesicles from hippocampal synapses. We report that CA1 pyramidal neurons and their synapses develop normally in the absence of astroglial Cx43. However, a significant impairment in synaptic vesicle distribution and release dynamics were observed. In particular, the FM1-43 assays performed using two-photon live imaging and combined with multi-electrode array stimulation in acute hippocampal slices, revealed a slower rate of synaptic vesicle release in Cx43−/− mice. Furthermore, paired-pulse recordings showed that synaptic vesicle release probability was also reduced and is dependent on glutamine supply via Cx43 hemichannel (HC). Taken together, we have uncovered a role for Cx43 in regulating presynaptic functions by controlling the rate and probability of synaptic vesicle release. Our findings further highlight the significance of astroglial Cx43 in synaptic transmission and efficacy. acknowledgement: 'This research was funded by grants from the European Research Council (Consolidator grant #683154) and European Union’s Horizon 2020 research and innovation program (Marie Sklodowska-Curie Innovative Training Networks, grant #722053, EU-GliaPhD) to N.R., as well as from FP7-PEOPLE Marie Curie Intra-European Fellowship for career development (grant #622289) to G.C. We thank Elena Dossi, Grégory Ghézali, and Jérémie Teillon for support with setting up the MEA system for the two-photon microscope. We would also like to thank Tayfun Palaz for their technical assistance with the EM preparations.' article_number: '1133' article_processing_charge: Yes article_type: original author: - first_name: Giselle T full_name: Cheung, Giselle T id: 471195F6-F248-11E8-B48F-1D18A9856A87 last_name: Cheung orcid: 0000-0001-8457-2572 - first_name: Oana full_name: Chever, Oana last_name: Chever - first_name: Astrid full_name: Rollenhagen, Astrid last_name: Rollenhagen - first_name: Nicole full_name: Quenech’du, Nicole last_name: Quenech’du - first_name: Pascal full_name: Ezan, Pascal last_name: Ezan - first_name: Joachim H. R. full_name: Lübke, Joachim H. R. last_name: Lübke - first_name: Nathalie full_name: Rouach, Nathalie last_name: Rouach citation: ama: Cheung GT, Chever O, Rollenhagen A, et al. Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses. Cells. 2023;12(8). doi:10.3390/cells12081133 apa: Cheung, G. T., Chever, O., Rollenhagen, A., Quenech’du, N., Ezan, P., Lübke, J. H. R., & Rouach, N. (2023). Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses. Cells. MDPI. https://doi.org/10.3390/cells12081133 chicago: Cheung, Giselle T, Oana Chever, Astrid Rollenhagen, Nicole Quenech’du, Pascal Ezan, Joachim H. R. Lübke, and Nathalie Rouach. “Astroglial Connexin 43 Regulates Synaptic Vesicle Release at Hippocampal Synapses.” Cells. MDPI, 2023. https://doi.org/10.3390/cells12081133. ieee: G. T. Cheung et al., “Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses,” Cells, vol. 12, no. 8. MDPI, 2023. ista: Cheung GT, Chever O, Rollenhagen A, Quenech’du N, Ezan P, Lübke JHR, Rouach N. 2023. Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses. Cells. 12(8), 1133. mla: Cheung, Giselle T., et al. “Astroglial Connexin 43 Regulates Synaptic Vesicle Release at Hippocampal Synapses.” Cells, vol. 12, no. 8, 1133, MDPI, 2023, doi:10.3390/cells12081133. short: G.T. Cheung, O. Chever, A. Rollenhagen, N. Quenech’du, P. Ezan, J.H.R. Lübke, N. Rouach, Cells 12 (2023). date_created: 2024-01-10T09:46:35Z date_published: 2023-04-11T00:00:00Z date_updated: 2024-01-16T09:29:35Z day: '11' ddc: - '570' department: - _id: SiHi doi: 10.3390/cells12081133 external_id: isi: - '000977445700001' pmid: - '37190042' file: - access_level: open_access checksum: 6798cd75d8857976fbc58a43fd173d68 content_type: application/pdf creator: dernst date_created: 2024-01-16T09:26:52Z date_updated: 2024-01-16T09:26:52Z file_id: '14808' file_name: 2023_Cells_Cheung.pdf file_size: 7931643 relation: main_file success: 1 file_date_updated: 2024-01-16T09:26:52Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '8' keyword: - General Medicine language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 publication: Cells publication_identifier: issn: - 2073-4409 publication_status: published publisher: MDPI quality_controlled: '1' status: public title: Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 12 year: '2023' ... --- _id: '12802' abstract: - lang: eng text: Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction. acknowledged_ssus: - _id: PreCl - _id: EM-Fac - _id: Bio - _id: LifeSc acknowledgement: We thank A. Freeman and V. Voronin for technical assistance, S. Deixler, A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal colony. We thank L. Andersen and J. Sonntag, who were involved in generating the MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance with the proteomic analysis, as well as the ISTA electron microscopy and Imaging and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated using Biorender.com. This work was supported by the Austrian Science Fund (FWF, DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Daniel full_name: Malzl, Daniel last_name: Malzl - first_name: Maria full_name: Gerykova Bujalkova, Maria last_name: Gerykova Bujalkova - first_name: Mateja full_name: Smogavec, Mateja last_name: Smogavec - first_name: Lena A. full_name: Schwarz, Lena A. last_name: Schwarz - first_name: Sarah full_name: Gorkiewicz, Sarah id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f last_name: Gorkiewicz - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Christian full_name: Knittl-Frank, Christian last_name: Knittl-Frank - first_name: Marianna full_name: Tassinari, Marianna id: 7af593f1-d44a-11ed-bf94-a3646a6bb35e last_name: Tassinari - first_name: Nuno full_name: Maulide, Nuno last_name: Maulide - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Jörg full_name: Menche, Jörg last_name: Menche - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037 apa: Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz, L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037 chicago: Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova, Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier, 2023. https://doi.org/10.1016/j.cell.2023.02.037. ieee: L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25, 2023. ista: Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25. mla: Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25, doi:10.1016/j.cell.2023.02.037. short: L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A. Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N. Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25. date_created: 2023-04-05T08:15:40Z date_published: 2023-04-27T00:00:00Z date_updated: 2024-02-07T08:03:32Z day: '27' ddc: - '570' department: - _id: SiHi - _id: GaNo doi: 10.1016/j.cell.2023.02.037 ec_funded: 1 external_id: isi: - '000991468700001' file: - access_level: open_access checksum: 47e94fbe19e86505b429cb7a5b503ce6 content_type: application/pdf creator: dernst date_created: 2023-05-02T09:26:21Z date_updated: 2023-05-02T09:26:21Z file_id: '12889' file_name: 2023_Cell_Knaus.pdf file_size: 15712841 relation: main_file success: 1 file_date_updated: 2023-05-02T09:26:21Z has_accepted_license: '1' intvolume: ' 186' isi: 1 issue: '9' keyword: - General Biochemistry - Genetics and Molecular Biology language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: 1950-1967.e25 project: - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models publication: Cell publication_identifier: issn: - 0092-8674 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/feed-them-or-lose-them/ record: - id: '13107' relation: dissertation_contains status: public scopus_import: '1' status: public title: Large neutral amino acid levels tune perinatal neuronal excitability and survival tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 186 year: '2023' ... --- _id: '11336' abstract: - lang: eng text: The generation of a correctly-sized cerebral cortex with all-embracing neuronal and glial cell-type diversity critically depends on faithful radial glial progenitor (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene expression instructs RGP lineage progression is unknown. Here we utilize Mosaic Analysis with Double Markers (MADM)-based single cell technology and demonstrate that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts at the global tissue-wide level. Conversely, cortical astrocyte production and maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation. We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression that are dependent on complex interplays between intrinsic and tissue-wide properties. In a broader context our results imply a critical role for the genetic and cellular niche environment in neural stem cell behavior. acknowledged_ssus: - _id: PreCl - _id: Bio - _id: LifeSc acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS Unit) and S. Gharagozlou for technical support. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A. received funding from the FWF Firnberg-Programm (T 1031). The work was supported by IST institutional funds and by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H. article_number: abq1263 article_processing_charge: No article_type: original author: - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. 2022;8(44). doi:10.1126/sciadv.abq1263 apa: Amberg, N., Pauler, F., Streicher, C., & Hippenmeyer, S. (2022). Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.abq1263 chicago: Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances. American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.abq1263. ieee: N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression,” Science Advances, vol. 8, no. 44. American Association for the Advancement of Science, 2022. ista: Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. 8(44), abq1263. mla: Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances, vol. 8, no. 44, abq1263, American Association for the Advancement of Science, 2022, doi:10.1126/sciadv.abq1263. short: N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022). date_created: 2022-04-26T15:04:50Z date_published: 2022-11-01T00:00:00Z date_updated: 2023-05-31T12:24:10Z day: '01' ddc: - '570' department: - _id: SiHi doi: 10.1126/sciadv.abq1263 ec_funded: 1 file: - access_level: open_access checksum: 0117023e188542082ca6693cf39e7f03 content_type: application/pdf creator: patrickd date_created: 2023-03-21T14:18:10Z date_updated: 2023-03-21T14:18:10Z file_id: '12742' file_name: sciadv.abq1263.pdf file_size: 2973998 relation: main_file success: 1 file_date_updated: 2023-03-21T14:18:10Z has_accepted_license: '1' intvolume: ' 8' issue: '44' language: - iso: eng month: '11' oa: 1 oa_version: Published Version project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression publication: Science Advances publication_identifier: issn: - 2375-2548 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' related_material: link: - description: News on ISTA website relation: press_release url: https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/ scopus_import: '1' status: public title: Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 8 year: '2022' ... --- _id: '9794' abstract: - lang: eng text: 'Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.' acknowledged_ssus: - _id: Bio - _id: EM-Fac - _id: PreCl - _id: LifeSc acknowledgement: This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013. article_processing_charge: No article_type: original author: - first_name: Frank P full_name: Assen, Frank P id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87 last_name: Assen orcid: 0000-0003-3470-6119 - first_name: Jun full_name: Abe, Jun last_name: Abe - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Tommaso full_name: Costanzo, Tommaso id: D93824F4-D9BA-11E9-BB12-F207E6697425 last_name: Costanzo orcid: 0000-0001-9732-3815 - first_name: Gabriel full_name: Krens, Gabriel id: 2B819732-F248-11E8-B48F-1D18A9856A87 last_name: Krens orcid: 0000-0003-4761-5996 - first_name: Markus full_name: Brown, Markus id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87 last_name: Brown - first_name: Burkhard full_name: Ludewig, Burkhard last_name: Ludewig - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 - first_name: Wolfgang full_name: Weninger, Wolfgang last_name: Weninger - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Sanjiv A. full_name: Luther, Sanjiv A. last_name: Luther - first_name: Jens V. full_name: Stein, Jens V. last_name: Stein - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-4561-241X citation: ama: Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4 apa: Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4 chicago: Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature, 2022. https://doi.org/10.1038/s41590-022-01257-4. ieee: F. P. Assen et al., “Multitier mechanics control stromal adaptations in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature, pp. 1246–1255, 2022. ista: Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255. mla: Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:10.1038/s41590-022-01257-4. short: F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255. date_created: 2021-08-06T09:09:11Z date_published: 2022-07-11T00:00:00Z date_updated: 2023-08-02T06:53:07Z day: '11' ddc: - '570' department: - _id: SiHi - _id: CaHe - _id: EdHa - _id: EM-Fac - _id: Bio - _id: MiSi doi: 10.1038/s41590-022-01257-4 ec_funded: 1 external_id: isi: - '000822975900002' file: - access_level: open_access checksum: 628e7b49809f22c75b428842efe70c68 content_type: application/pdf creator: dernst date_created: 2022-07-25T07:11:32Z date_updated: 2022-07-25T07:11:32Z file_id: '11642' file_name: 2022_NatureImmunology_Assen.pdf file_size: 11475325 relation: main_file success: 1 file_date_updated: 2022-07-25T07:11:32Z has_accepted_license: '1' intvolume: ' 23' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1246-1255 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: Nature Immunology publication_identifier: eissn: - 1529-2916 issn: - 1529-2908 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Multitier mechanics control stromal adaptations in swelling lymph nodes tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 23 year: '2022' ... --- _id: '10764' abstract: - lang: eng text: Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a fluorescent probe that tracks glutamine in live cells, which provides direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes. acknowledgement: 'We thank D. Mazaud and. J. Cazères for technical assistance. This work was supported by grants from the European Research Council (Consolidator grant #683154) and European Union’s Horizon 2020 research and innovation program (Marie Sklodowska-Curie Innovative Training Networks, grant #722053, EU-GliaPhD) to N.R. and from FP7-PEOPLE Marie Curie Intra-European Fellowship for career development (grant #622289) to G.C.' article_number: '753' article_processing_charge: No article_type: original author: - first_name: Giselle T full_name: Cheung, Giselle T id: 471195F6-F248-11E8-B48F-1D18A9856A87 last_name: Cheung - first_name: Danijela full_name: Bataveljic, Danijela last_name: Bataveljic - first_name: Josien full_name: Visser, Josien last_name: Visser - first_name: Naresh full_name: Kumar, Naresh last_name: Kumar - first_name: Julien full_name: Moulard, Julien last_name: Moulard - first_name: Glenn full_name: Dallérac, Glenn last_name: Dallérac - first_name: Daria full_name: Mozheiko, Daria last_name: Mozheiko - first_name: Astrid full_name: Rollenhagen, Astrid last_name: Rollenhagen - first_name: Pascal full_name: Ezan, Pascal last_name: Ezan - first_name: Cédric full_name: Mongin, Cédric last_name: Mongin - first_name: Oana full_name: Chever, Oana last_name: Chever - first_name: Alexis Pierre full_name: Bemelmans, Alexis Pierre last_name: Bemelmans - first_name: Joachim full_name: Lübke, Joachim last_name: Lübke - first_name: Isabelle full_name: Leray, Isabelle last_name: Leray - first_name: Nathalie full_name: Rouach, Nathalie last_name: Rouach citation: ama: Cheung GT, Bataveljic D, Visser J, et al. Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. 2022;13. doi:10.1038/s41467-022-28331-7 apa: Cheung, G. T., Bataveljic, D., Visser, J., Kumar, N., Moulard, J., Dallérac, G., … Rouach, N. (2022). Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28331-7 chicago: Cheung, Giselle T, Danijela Bataveljic, Josien Visser, Naresh Kumar, Julien Moulard, Glenn Dallérac, Daria Mozheiko, et al. “Physiological Synaptic Activity and Recognition Memory Require Astroglial Glutamine.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28331-7. ieee: G. T. Cheung et al., “Physiological synaptic activity and recognition memory require astroglial glutamine,” Nature Communications, vol. 13. Springer Nature, 2022. ista: Cheung GT, Bataveljic D, Visser J, Kumar N, Moulard J, Dallérac G, Mozheiko D, Rollenhagen A, Ezan P, Mongin C, Chever O, Bemelmans AP, Lübke J, Leray I, Rouach N. 2022. Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. 13, 753. mla: Cheung, Giselle T., et al. “Physiological Synaptic Activity and Recognition Memory Require Astroglial Glutamine.” Nature Communications, vol. 13, 753, Springer Nature, 2022, doi:10.1038/s41467-022-28331-7. short: G.T. Cheung, D. Bataveljic, J. Visser, N. Kumar, J. Moulard, G. Dallérac, D. Mozheiko, A. Rollenhagen, P. Ezan, C. Mongin, O. Chever, A.P. Bemelmans, J. Lübke, I. Leray, N. Rouach, Nature Communications 13 (2022). date_created: 2022-02-20T23:01:30Z date_published: 2022-02-08T00:00:00Z date_updated: 2023-08-02T14:25:01Z day: '08' ddc: - '570' department: - _id: SiHi doi: 10.1038/s41467-022-28331-7 external_id: isi: - '000757297200017' pmid: - '35136061' file: - access_level: open_access checksum: 51d580aff2327dd957946208a9749e1a content_type: application/pdf creator: dernst date_created: 2022-02-21T07:51:33Z date_updated: 2022-02-21T07:51:33Z file_id: '10777' file_name: 2022_NatureCommunications_Cheung.pdf file_size: 7910519 relation: main_file success: 1 file_date_updated: 2022-02-21T07:51:33Z has_accepted_license: '1' intvolume: ' 13' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - '20411723' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Physiological synaptic activity and recognition memory require astroglial glutamine tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2022' ... --- _id: '11460' abstract: - lang: eng text: "Background: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology.\r\nMethods: Here, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques.\r\nResults: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages.\r\nLimitations: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation.\r\nConclusions: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life." acknowledgement: "This study was funded by NIMH R21MH115347 to KSZ. KSZ is further supported by Shriners Hospitals for Children.\r\nWe would like to thank Angelo Harlan de Crescenzo for early contributions to this project." article_number: '27' article_processing_charge: No article_type: original author: - first_name: Zachary A. full_name: Schaaf, Zachary A. last_name: Schaaf - first_name: Lyvin full_name: Tat, Lyvin last_name: Tat - first_name: Noemi full_name: Cannizzaro, Noemi last_name: Cannizzaro - first_name: Ralph full_name: Green, Ralph last_name: Green - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Konstantinos S. full_name: Zarbalis, Konstantinos S. last_name: Zarbalis citation: ama: Schaaf ZA, Tat L, Cannizzaro N, et al. WDFY3 mutation alters laminar position and morphology of cortical neurons. Molecular Autism. 2022;13. doi:10.1186/s13229-022-00508-3 apa: Schaaf, Z. A., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S., & Zarbalis, K. S. (2022). WDFY3 mutation alters laminar position and morphology of cortical neurons. Molecular Autism. Springer Nature. https://doi.org/10.1186/s13229-022-00508-3 chicago: Schaaf, Zachary A., Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke, Simon Hippenmeyer, and Konstantinos S. Zarbalis. “WDFY3 Mutation Alters Laminar Position and Morphology of Cortical Neurons.” Molecular Autism. Springer Nature, 2022. https://doi.org/10.1186/s13229-022-00508-3. ieee: Z. A. Schaaf et al., “WDFY3 mutation alters laminar position and morphology of cortical neurons,” Molecular Autism, vol. 13. Springer Nature, 2022. ista: Schaaf ZA, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis KS. 2022. WDFY3 mutation alters laminar position and morphology of cortical neurons. Molecular Autism. 13, 27. mla: Schaaf, Zachary A., et al. “WDFY3 Mutation Alters Laminar Position and Morphology of Cortical Neurons.” Molecular Autism, vol. 13, 27, Springer Nature, 2022, doi:10.1186/s13229-022-00508-3. short: Z.A. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K.S. Zarbalis, Molecular Autism 13 (2022). date_created: 2022-06-23T14:28:55Z date_published: 2022-06-22T00:00:00Z date_updated: 2023-08-03T07:21:32Z day: '22' ddc: - '570' department: - _id: SiHi doi: 10.1186/s13229-022-00508-3 external_id: isi: - '000814641400001' file: - access_level: open_access checksum: 525d2618e855139089bbfc3e3d49d1b2 content_type: application/pdf creator: dernst date_created: 2022-06-24T08:22:59Z date_updated: 2022-06-24T08:22:59Z file_id: '11461' file_name: 2022_MolecularAutism_Schaaf.pdf file_size: 7552298 relation: main_file success: 1 file_date_updated: 2022-06-24T08:22:59Z has_accepted_license: '1' intvolume: ' 13' isi: 1 keyword: - Psychiatry and Mental health - Developmental Biology - Developmental Neuroscience - Molecular Biology language: - iso: eng month: '06' oa: 1 oa_version: Published Version publication: Molecular Autism publication_identifier: issn: - 2040-2392 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: erratum url: https://doi.org/10.1186/s13229-023-00539-4 status: public title: WDFY3 mutation alters laminar position and morphology of cortical neurons tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2022' ... --- _id: '11449' abstract: - lang: eng text: Mutations are acquired frequently, such that each cell's genome inscribes its history of cell divisions. Common genomic alterations involve loss of heterozygosity (LOH). LOH accumulates throughout the genome, offering large encoding capacity for inferring cell lineage. Using only single-cell RNA sequencing (scRNA-seq) of mouse brain cells, we found that LOH events spanning multiple genes are revealed as tracts of monoallelically expressed, constitutionally heterozygous single-nucleotide variants (SNVs). We simultaneously inferred cell lineage and marked developmental time points based on X chromosome inactivation and the total number of LOH events while identifying cell types from gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. This type of retrospective analysis could be incorporated into scRNA-seq pipelines and, compared with experimental approaches for determining lineage in model organisms, is applicable where genetic engineering is prohibited, such as humans. acknowledgement: D.J.A. thanks Wayne K. Potts, Alan R. Rogers, Kristen Hawkes, Ryk Ward, and Jon Seger for inspiring a young undergraduate to apply evolutionary theory to intraorganism development. Supported by the Paul G. Allen Frontiers Group (University of Washington); NIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program 725780 LinPro to S.H. article_processing_charge: No article_type: original author: - first_name: Donovan J. full_name: Anderson, Donovan J. last_name: Anderson - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler - first_name: Aaron full_name: Mckenna, Aaron last_name: Mckenna - first_name: Jay full_name: Shendure, Jay last_name: Shendure - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Marshall S. full_name: Horwitz, Marshall S. last_name: Horwitz citation: ama: Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. 2022;13(6):438-453.e5. doi:10.1016/j.cels.2022.03.006 apa: Anderson, D. J., Pauler, F., Mckenna, A., Shendure, J., Hippenmeyer, S., & Horwitz, M. S. (2022). Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. Elsevier. https://doi.org/10.1016/j.cels.2022.03.006 chicago: Anderson, Donovan J., Florian Pauler, Aaron Mckenna, Jay Shendure, Simon Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems. Elsevier, 2022. https://doi.org/10.1016/j.cels.2022.03.006. ieee: D. J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, and M. S. Horwitz, “Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development,” Cell Systems, vol. 13, no. 6. Elsevier, p. 438–453.e5, 2022. ista: Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. 2022. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. 13(6), 438–453.e5. mla: Anderson, Donovan J., et al. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems, vol. 13, no. 6, Elsevier, 2022, p. 438–453.e5, doi:10.1016/j.cels.2022.03.006. short: D.J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, Cell Systems 13 (2022) 438–453.e5. date_created: 2022-06-19T22:01:57Z date_published: 2022-06-15T00:00:00Z date_updated: 2023-08-03T07:19:43Z day: '15' department: - _id: SiHi doi: 10.1016/j.cels.2022.03.006 ec_funded: 1 external_id: isi: - '000814124400002' pmid: - '35452605' intvolume: ' 13' isi: 1 issue: '6' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.cels.2022.03.006 month: '06' oa: 1 oa_version: Published Version page: 438-453.e5 pmid: 1 project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development - _id: 25D92700-B435-11E9-9278-68D0E5697425 grant_number: LS13-002 name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain publication: Cell Systems publication_identifier: eissn: - 2405-4720 issn: - 2405-4712 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2022' ... --- _id: '12283' abstract: - lang: eng text: Neurons extend axons to form the complex circuitry of the mature brain. This depends on the coordinated response and continuous remodelling of the microtubule and F-actin networks in the axonal growth cone. Growth cone architecture remains poorly understood at nanoscales. We therefore investigated mouse hippocampal neuron growth cones using cryo-electron tomography to directly visualise their three-dimensional subcellular architecture with molecular detail. Our data showed that the hexagonal arrays of actin bundles that form filopodia penetrate and terminate deep within the growth cone interior. We directly observed the modulation of these and other growth cone actin bundles by alteration of individual F-actin helical structures. Microtubules with blunt, slightly flared or gently curved ends predominated in the growth cone, frequently contained lumenal particles and exhibited lattice defects. Investigation of the effect of absence of doublecortin, a neurodevelopmental cytoskeleton regulator, on growth cone cytoskeleton showed no major anomalies in overall growth cone organisation or in F-actin subpopulations. However, our data suggested that microtubules sustained more structural defects, highlighting the importance of microtubule integrity during growth cone migration. acknowledgement: "J.A. was supported by a grant from the Medical Research Council (MRC), UK (MR/R000352/1) to C.A.M. Cryo-EM data were collected on equipment funded by the Wellcome Trust, UK (079605/Z/06/Z) and the Biotechnology and Biological Sciences Research Council (BBSRC) UK (BB/L014211/1). F.F.’s salary and institute were supported by Inserm (Institut National de la Santé et de la Recherche Médicale), CNRS (Centre National de la Recherche Scientifique) and Sorbonne Université. F.F.’s group was particularly supported by Agence Nationale de la\r\nRecherche (ANR-16-CE16-0011-03) and Seventh Framework Programme (EUHEALTH-\r\n2013, DESIRE, N° 60253; also funding M.S.’s salary) and the European Cooperation in Science and Technology (COST Action CA16118). Open Access funding provided by Birkbeck College: Birkbeck University of London. Deposited in PMC for immediate release." article_number: '259234' article_processing_charge: No article_type: original author: - first_name: Joseph full_name: Atherton, Joseph last_name: Atherton - first_name: Melissa A full_name: Stouffer, Melissa A id: 4C9372C4-F248-11E8-B48F-1D18A9856A87 last_name: Stouffer - first_name: Fiona full_name: Francis, Fiona last_name: Francis - first_name: Carolyn A. full_name: Moores, Carolyn A. last_name: Moores citation: ama: Atherton J, Stouffer MA, Francis F, Moores CA. Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. Journal of Cell Science. 2022;135(7). doi:10.1242/jcs.259234 apa: Atherton, J., Stouffer, M. A., Francis, F., & Moores, C. A. (2022). Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.259234 chicago: Atherton, Joseph, Melissa A Stouffer, Fiona Francis, and Carolyn A. Moores. “Visualising the Cytoskeletal Machinery in Neuronal Growth Cones Using Cryo-Electron Tomography.” Journal of Cell Science. The Company of Biologists, 2022. https://doi.org/10.1242/jcs.259234. ieee: J. Atherton, M. A. Stouffer, F. Francis, and C. A. Moores, “Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography,” Journal of Cell Science, vol. 135, no. 7. The Company of Biologists, 2022. ista: Atherton J, Stouffer MA, Francis F, Moores CA. 2022. Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. Journal of Cell Science. 135(7), 259234. mla: Atherton, Joseph, et al. “Visualising the Cytoskeletal Machinery in Neuronal Growth Cones Using Cryo-Electron Tomography.” Journal of Cell Science, vol. 135, no. 7, 259234, The Company of Biologists, 2022, doi:10.1242/jcs.259234. short: J. Atherton, M.A. Stouffer, F. Francis, C.A. Moores, Journal of Cell Science 135 (2022). date_created: 2023-01-16T10:03:24Z date_published: 2022-04-01T00:00:00Z date_updated: 2023-08-04T10:28:34Z day: '01' ddc: - '570' department: - _id: SiHi doi: 10.1242/jcs.259234 external_id: isi: - '000783840400010' pmid: - '35383828' file: - access_level: open_access checksum: 4346ed32cb7c89a8ca051c7da68a9a1c content_type: application/pdf creator: dernst date_created: 2023-01-30T11:41:01Z date_updated: 2023-01-30T11:41:01Z file_id: '12461' file_name: 2022_JourCellBiology_Atherton.pdf file_size: 13868733 relation: main_file success: 1 file_date_updated: 2023-01-30T11:41:01Z has_accepted_license: '1' intvolume: ' 135' isi: 1 issue: '7' keyword: - Cell Biology language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 publication: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - 0021-9533 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 135 year: '2022' ... --- _id: '12282' abstract: - lang: eng text: From a simple thought to a multicellular movement acknowledgement: The authors want to thank Professors Carrie Bernecky, Tom Henzinger, Martin Loose and Gaia Novarino for accepting to be interviewed, thus giving significant contribution to the discussion that lead to this article. article_number: '260017' article_processing_charge: No article_type: letter_note author: - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Melissa A full_name: Stouffer, Melissa A id: 4C9372C4-F248-11E8-B48F-1D18A9856A87 last_name: Stouffer - first_name: Irene full_name: Vercellino, Irene id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87 last_name: Vercellino orcid: 0000-0001-5618-3449 citation: ama: Amberg N, Stouffer MA, Vercellino I. Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. 2022;135(8). doi:10.1242/jcs.260017 apa: Amberg, N., Stouffer, M. A., & Vercellino, I. (2022). Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.260017 chicago: Amberg, Nicole, Melissa A Stouffer, and Irene Vercellino. “Operation STEM Fatale – How an Equity, Diversity and Inclusion Initiative Has Brought Us to Reflect on the Current Challenges in Cell Biology and Science as a Whole.” Journal of Cell Science. The Company of Biologists, 2022. https://doi.org/10.1242/jcs.260017. ieee: N. Amberg, M. A. Stouffer, and I. Vercellino, “Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole,” Journal of Cell Science, vol. 135, no. 8. The Company of Biologists, 2022. ista: Amberg N, Stouffer MA, Vercellino I. 2022. Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. 135(8), 260017. mla: Amberg, Nicole, et al. “Operation STEM Fatale – How an Equity, Diversity and Inclusion Initiative Has Brought Us to Reflect on the Current Challenges in Cell Biology and Science as a Whole.” Journal of Cell Science, vol. 135, no. 8, 260017, The Company of Biologists, 2022, doi:10.1242/jcs.260017. short: N. Amberg, M.A. Stouffer, I. Vercellino, Journal of Cell Science 135 (2022). date_created: 2023-01-16T10:03:14Z date_published: 2022-04-19T00:00:00Z date_updated: 2023-08-04T10:28:04Z day: '19' department: - _id: SiHi - _id: LeSa doi: 10.1242/jcs.260017 external_id: isi: - '000798123600015' pmid: - '35438168' intvolume: ' 135' isi: 1 issue: '8' language: - iso: eng month: '04' oa_version: None pmid: 1 publication: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - 0021-9533 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 135 year: '2022' ... --- _id: '10792' abstract: - lang: eng text: "Background\r\nProper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology .\r\nMethods\r\nHere, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild type cells concomitantly in vivo using immunofluorescent techniques.\r\nResults\r\nWe revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. Limitations While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients.\r\nConclusions\r\n\uFEFFOur genetic approach revealed several cell autonomous requirements of Wdfy3 in neuronal development that could underly the pathogenic mechanisms of WDFY3-related ASD conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for Wdfy3 in regulating neuronal function and interconnectivity in postnatal life." article_processing_charge: No author: - first_name: Zachary full_name: Schaaf, Zachary last_name: Schaaf - first_name: Lyvin full_name: Tat, Lyvin last_name: Tat - first_name: Noemi full_name: Cannizzaro, Noemi last_name: Cannizzaro - first_name: Ralph full_name: Green, Ralph last_name: Green - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: K full_name: Zarbalis, K last_name: Zarbalis citation: ama: Schaaf Z, Tat L, Cannizzaro N, et al. WDFY3 cell autonomously controls neuronal migration. doi:10.21203/rs.3.rs-1316167/v1 apa: Schaaf, Z., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S., & Zarbalis, K. (n.d.). WDFY3 cell autonomously controls neuronal migration. Research Square. https://doi.org/10.21203/rs.3.rs-1316167/v1 chicago: Schaaf, Zachary, Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke, Simon Hippenmeyer, and K Zarbalis. “WDFY3 Cell Autonomously Controls Neuronal Migration.” Research Square, n.d. https://doi.org/10.21203/rs.3.rs-1316167/v1. ieee: Z. Schaaf et al., “WDFY3 cell autonomously controls neuronal migration.” Research Square. ista: Schaaf Z, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis K. WDFY3 cell autonomously controls neuronal migration. 10.21203/rs.3.rs-1316167/v1. mla: Schaaf, Zachary, et al. WDFY3 Cell Autonomously Controls Neuronal Migration. Research Square, doi:10.21203/rs.3.rs-1316167/v1. short: Z. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K. Zarbalis, (n.d.). date_created: 2022-02-25T07:53:26Z date_published: 2022-02-16T00:00:00Z date_updated: 2023-10-17T13:06:52Z day: '16' department: - _id: SiHi doi: 10.21203/rs.3.rs-1316167/v1 external_id: pmid: - PPR454733 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.21203/rs.3.rs-1316167/v1 month: '02' oa: 1 oa_version: Preprint page: '30' pmid: 1 publication_identifier: eissn: - 2693-5015 publication_status: submitted publisher: Research Square status: public title: WDFY3 cell autonomously controls neuronal migration tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '10791' abstract: - lang: eng text: The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general. acknowledged_ssus: - _id: LifeSc - _id: PreCl - _id: Bio acknowledgement: "A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility." article_number: kvac009 article_processing_charge: No article_type: original author: - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Michael full_name: Riedl, Michael id: 3BE60946-F248-11E8-B48F-1D18A9856A87 last_name: Riedl orcid: 0000-0003-4844-6311 - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Anna-Magdalena full_name: Heger, Anna-Magdalena id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87 last_name: Heger - first_name: Susanne full_name: Laukoter, Susanne id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87 last_name: Laukoter orcid: 0000-0002-7903-3010 - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 - first_name: Li Huei full_name: Tsai, Li Huei last_name: Tsai - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1). doi:10.1093/oons/kvac009 apa: Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. Oxford Academic. https://doi.org/10.1093/oons/kvac009 chicago: Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience. Oxford Academic, 2022. https://doi.org/10.1093/oons/kvac009. ieee: A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” Oxford Open Neuroscience, vol. 1, no. 1. Oxford Academic, 2022. ista: Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009. mla: Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009, Oxford Academic, 2022, doi:10.1093/oons/kvac009. short: A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022). date_created: 2022-02-25T07:52:11Z date_published: 2022-07-07T00:00:00Z date_updated: 2023-11-30T10:55:12Z day: '07' ddc: - '570' department: - _id: SiHi - _id: BjHo - _id: LifeSc - _id: EM-Fac doi: 10.1093/oons/kvac009 ec_funded: 1 file: - access_level: open_access checksum: 822e76e056c07099d1fb27d1ece5941b content_type: application/pdf creator: dernst date_created: 2023-08-16T08:00:30Z date_updated: 2023-08-16T08:00:30Z file_id: '14061' file_name: 2023_OxfordOpenNeuroscience_Hansen.pdf file_size: 4846551 relation: main_file success: 1 file_date_updated: 2023-08-16T08:00:30Z has_accepted_license: '1' intvolume: ' 1' issue: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version project: - _id: 25D61E48-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618444' name: Molecular Mechanisms of Cerebral Cortex Development - _id: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration publication: Oxford Open Neuroscience publication_identifier: eissn: - 2753-149X publication_status: published publisher: Oxford Academic quality_controlled: '1' related_material: record: - id: '12726' relation: dissertation_contains status: public - id: '14530' relation: dissertation_contains status: public status: public title: Tissue-wide effects override cell-intrinsic gene function in radial neuron migration tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1 year: '2022' ... --- _id: '9082' abstract: - lang: eng text: Acquired mutations are sufficiently frequent such that the genome of a single cell offers a record of its history of cell divisions. Among more common somatic genomic alterations are loss of heterozygosity (LOH). Large LOH events are potentially detectable in single cell RNA sequencing (scRNA-seq) datasets as tracts of monoallelic expression for constitutionally heterozygous single nucleotide variants (SNVs) located among contiguous genes. We identified runs of monoallelic expression, consistent with LOH, uniquely distributed throughout the genome in single cell brain cortex transcriptomes of F1 hybrids involving different inbred mouse strains. We then phylogenetically reconstructed single cell lineages and simultaneously identified cell types by corresponding gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. Compared to engineered recording systems, LOH events accumulate throughout the genome and across the lifetime of an organism, affording tremendous capacity for encoding lineage information and increasing resolution for later cell divisions. This approach can conceivably be computationally incorporated into scRNA-seq analysis and may be useful for organisms where genetic engineering is prohibitive, such as humans. acknowledgement: "We thank Bill Bolosky, Microsoft Research, for earlier work showing proof of concept in TCGA\r\nbulk RNA-seq data. Supported by the Paul G. Allen Frontiers Group (University of Washington);\r\nNIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b] life science call grant\r\n(C13-002) to SH, and the European Research Council (ERC) under the European Union’s\r\nHorizon 2020 research and innovation program 725780 LinPro to SH." article_processing_charge: No author: - first_name: Donovan J. full_name: Anderson, Donovan J. last_name: Anderson - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler - first_name: Aaron full_name: McKenna, Aaron last_name: McKenna - first_name: Jay full_name: Shendure, Jay last_name: Shendure - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Marshall S. full_name: Horwitz, Marshall S. last_name: Horwitz citation: ama: Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. bioRxiv. doi:10.1101/2020.12.31.425016 apa: Anderson, D. J., Pauler, F., McKenna, A., Shendure, J., Hippenmeyer, S., & Horwitz, M. S. (n.d.). Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.12.31.425016 chicago: Anderson, Donovan J., Florian Pauler, Aaron McKenna, Jay Shendure, Simon Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Identification of Brain Cell Type and Lineage via Single Cell RNA Sequencing.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.12.31.425016. ieee: D. J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, and M. S. Horwitz, “Simultaneous identification of brain cell type and lineage via single cell RNA sequencing,” bioRxiv. Cold Spring Harbor Laboratory. ista: Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. bioRxiv, 10.1101/2020.12.31.425016. mla: Anderson, Donovan J., et al. “Simultaneous Identification of Brain Cell Type and Lineage via Single Cell RNA Sequencing.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.12.31.425016. short: D.J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, BioRxiv (n.d.). date_created: 2021-02-04T07:23:23Z date_published: 2021-01-01T00:00:00Z date_updated: 2021-02-04T07:29:53Z day: '01' department: - _id: SiHi doi: 10.1101/2020.12.31.425016 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.12.31.425016 month: '01' oa: 1 oa_version: Preprint project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory status: public title: Simultaneous identification of brain cell type and lineage via single cell RNA sequencing type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2021' ...