[{"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"}],"issue":"1","type":"journal_article","oa_version":"Published Version","_id":"14794","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers","status":"public","intvolume":" 5","day":"01","article_processing_charge":"Yes","scopus_import":"1","date_published":"2024-01-01T00:00:00Z","publication":"STAR Protocols","citation":{"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.","short":"A.H. Hansen, S. Hippenmeyer, STAR Protocols 5 (2024).","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.","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","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.","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"},"article_type":"review","article_number":"102795","author":[{"full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen"},{"full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"link":[{"url":"http://github.com/hippenmeyerlab","relation":"software"}]},"date_updated":"2024-01-17T10:32:31Z","date_created":"2024-01-14T23:00:56Z","volume":5,"year":"2024","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.","pmid":1,"publication_status":"epub_ahead","department":[{"_id":"SiHi"}],"publisher":"Elsevier","month":"01","publication_identifier":{"eissn":["2666-1667"]},"doi":"10.1016/j.xpro.2023.102795","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"language":[{"iso":"eng"}],"oa":1,"external_id":{"pmid":["38165800"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.xpro.2023.102795"}],"quality_controlled":"1","project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration"}]},{"month":"01","publication_identifier":{"issn":["0896-6273"]},"doi":"10.1016/j.neuron.2023.11.009","acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"PreCl"}],"language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["38096816"]},"oa":1,"quality_controlled":"1","project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F07805","name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"file_date_updated":"2024-02-06T13:56:15Z","author":[{"full_name":"Cheung, Giselle T","last_name":"Cheung","first_name":"Giselle T","orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian"},{"last_name":"Koppensteiner","first_name":"Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter"},{"first_name":"Thomas","last_name":"Krausgruber","full_name":"Krausgruber, Thomas"},{"last_name":"Streicher","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"full_name":"Schrammel, Martin","last_name":"Schrammel","first_name":"Martin","id":"f13e7cae-e8bd-11ed-841a-96dedf69f46d"},{"id":"e68ece33-f6e0-11ea-865d-ae1031dcc090","last_name":"Özgen","first_name":"Natalie Y","full_name":"Özgen, Natalie Y"},{"full_name":"Ivec, Alexis","first_name":"Alexis","last_name":"Ivec","id":"1d144691-e8be-11ed-9b33-bdd3077fad4c"},{"first_name":"Christoph","last_name":"Bock","full_name":"Bock, Christoph"},{"last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon"}],"related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-pedigree-of-brain-cells/","relation":"press_release","description":"News on ISTA Website"}]},"date_updated":"2024-03-05T09:43:02Z","date_created":"2023-04-27T09:41:48Z","volume":112,"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. ","year":"2024","pmid":1,"publication_status":"published","department":[{"_id":"SiHi"},{"_id":"RySh"}],"publisher":"Elsevier","day":"17","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","scopus_import":"1","date_published":"2024-01-17T00:00:00Z","publication":"Neuron","citation":{"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.","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.","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","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.","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","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."},"article_type":"original","page":"230-246.e11","abstract":[{"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.","lang":"eng"}],"issue":"2","type":"journal_article","file":[{"relation":"main_file","file_id":"14944","date_updated":"2024-02-06T13:56:15Z","date_created":"2024-02-06T13:56:15Z","checksum":"32b3788f7085cf44a84108d8faaff3ce","success":1,"file_name":"2024_Neuron_Cheung.pdf","access_level":"open_access","content_type":"application/pdf","file_size":5942467,"creator":"dernst"}],"oa_version":"Published Version","_id":"12875","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Multipotent progenitors instruct ontogeny of the superior colliculus","status":"public","ddc":["570"],"intvolume":" 112"},{"month":"02","publication_identifier":{"eissn":["1097-4199"]},"quality_controlled":"1","isi":1,"external_id":{"isi":["000994473300001"]},"language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2023.01.006","publication_status":"published","department":[{"_id":"SiHi"}],"publisher":"Elsevier","year":"2023","date_created":"2023-02-12T23:00:58Z","date_updated":"2023-08-01T13:10:27Z","volume":111,"author":[{"id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","orcid":"0000-0002-5615-5277","first_name":"Ana","last_name":"Villalba Requena","full_name":"Villalba Requena, Ana"},{"full_name":"Hippenmeyer, Simon","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061"}],"scopus_import":"1","day":"01","article_processing_charge":"No","article_type":"letter_note","page":"291-293","publication":"Neuron","citation":{"short":"A. Villalba Requena, S. Hippenmeyer, Neuron 111 (2023) 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.","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.","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","ieee":"A. Villalba Requena and S. Hippenmeyer, “Going back in time with TEMPO,” Neuron, vol. 111, no. 3. Elsevier, pp. 291–293, 2023.","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","ista":"Villalba Requena A, Hippenmeyer S. 2023. Going back in time with TEMPO. Neuron. 111(3), 291–293."},"date_published":"2023-02-01T00:00:00Z","type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"3","title":"Going back in time with TEMPO","status":"public","intvolume":" 111","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12542","oa_version":"None"},{"article_number":"102695","ec_funded":1,"file_date_updated":"2023-08-16T12:29:06Z","pmid":1,"year":"2023","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.","publisher":"Elsevier","department":[{"_id":"SiHi"}],"publication_status":"published","author":[{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon"}],"volume":79,"date_created":"2023-02-26T12:24:21Z","date_updated":"2023-08-16T12:30:25Z","publication_identifier":{"issn":["0959-4388"]},"month":"04","external_id":{"pmid":["36842274"],"isi":["000953497700001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F07805","name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780"}],"isi":1,"quality_controlled":"1","doi":"10.1016/j.conb.2023.102695","language":[{"iso":"eng"}],"type":"journal_article","issue":"4","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."}],"_id":"12679","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 79","status":"public","title":"Principles of neural stem cell lineage progression: Insights from developing cerebral cortex","ddc":["570"],"oa_version":"Published Version","file":[{"date_created":"2023-08-16T12:29:06Z","date_updated":"2023-08-16T12:29:06Z","success":1,"checksum":"4d11c4ca87e6cbc4d2ac46d3225ea615","file_id":"14071","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":1787894,"file_name":"2023_CurrentOpinionNeurobio_Hippenmeyer.pdf","access_level":"open_access"}],"scopus_import":"1","keyword":["General Neuroscience"],"has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","day":"01","citation":{"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.","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","ista":"Hippenmeyer S. 2023. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. Current Opinion in Neurobiology. 79(4), 102695.","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","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.","short":"S. Hippenmeyer, Current Opinion in Neurobiology 79 (2023).","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."},"publication":"Current Opinion in Neurobiology","article_type":"review","date_published":"2023-04-01T00:00:00Z"},{"issue":"3","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."}],"type":"journal_article","oa_version":"None","_id":"12562","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 129","title":"Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons","status":"public","article_processing_charge":"No","day":"01","keyword":["Physiology","General Neuroscience"],"date_published":"2023-03-01T00:00:00Z","citation":{"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.","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.","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","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.","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","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."},"publication":"Journal of Neurophysiology","page":"501-512","article_type":"original","author":[{"full_name":"Ladle, David R.","first_name":"David R.","last_name":"Ladle"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon"}],"volume":129,"date_created":"2023-02-15T14:46:14Z","date_updated":"2023-09-05T12:13:34Z","pmid":1,"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.","year":"2023","publisher":"American Physiological Society","department":[{"_id":"SiHi"}],"publication_status":"published","publication_identifier":{"issn":["0022-3077"],"eissn":["1522-1598"]},"month":"03","doi":"10.1152/jn.00172.2022","language":[{"iso":"eng"}],"external_id":{"pmid":["36695533"],"isi":["000957721600001"]},"quality_controlled":"1","isi":1},{"abstract":[{"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.","lang":"eng"}],"type":"preprint","author":[{"full_name":"Bose, Mahima","first_name":"Mahima","last_name":"Bose"},{"full_name":"Suresh, Varun","last_name":"Suresh","first_name":"Varun"},{"full_name":"Mishra, Urvi","first_name":"Urvi","last_name":"Mishra"},{"full_name":"Talwar, Ishita","last_name":"Talwar","first_name":"Ishita"},{"last_name":"Yadav","first_name":"Anuradha","full_name":"Yadav, Anuradha"},{"full_name":"Biswas, Shiona","first_name":"Shiona","last_name":"Biswas"},{"first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"},{"last_name":"Tole","first_name":"Shubha","full_name":"Tole, Shubha"}],"oa_version":"Preprint","date_updated":"2023-12-11T07:37:17Z","date_created":"2023-12-06T13:07:01Z","_id":"14647","year":"2023","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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).","publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"SiHi"}],"publication_status":"submitted","title":"Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway","status":"public","article_processing_charge":"No","month":"12","day":"01","date_published":"2023-12-01T00:00:00Z","doi":"10.1101/2023.11.30.569337","language":[{"iso":"eng"}],"citation":{"short":"M. Bose, V. Suresh, U. Mishra, I. Talwar, A. Yadav, S. Biswas, S. Hippenmeyer, S. Tole, BioRxiv (n.d.).","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.","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.","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","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.","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","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."},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2023.11.30.569337","open_access":"1"}],"publication":"bioRxiv"},{"author":[{"first_name":"Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"first_name":"Giselle T","last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T"},{"first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"volume":5,"date_created":"2023-12-13T11:48:05Z","date_updated":"2023-12-18T08:06:14Z","pmid":1,"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.","year":"2023","publisher":"Elsevier","department":[{"_id":"SiHi"}],"publication_status":"epub_ahead","ec_funded":1,"article_number":"102771","doi":"10.1016/j.xpro.2023.102771","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["38070137"]},"main_file_link":[{"url":"https://doi.org/10.1016/j.xpro.2023.102771","open_access":"1"}],"oa":1,"project":[{"call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T0101031"},{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F07805"},{"call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","publication_identifier":{"issn":["2666-1667"]},"month":"12","oa_version":"Submitted Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14683","intvolume":" 5","ddc":["570"],"status":"public","title":"Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry","issue":"1","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"}],"type":"journal_article","date_published":"2023-12-08T00:00:00Z","citation":{"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.","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).","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.","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.","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","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"},"publication":"STAR Protocols","article_type":"review","article_processing_charge":"No","day":"08","scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"]},{"page":"169-191","quality_controlled":"1","citation":{"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.","short":"A. Villalba Requena, N. Amberg, S. Hippenmeyer, in:, W. Huttner (Ed.), Neocortical Neurogenesis in Development and Evolution, Wiley, 2023, pp. 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.","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","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.","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"},"publication":"Neocortical Neurogenesis in Development and Evolution","language":[{"iso":"eng"}],"date_published":"2023-08-08T00:00:00Z","doi":"10.1002/9781119860914.ch10","scopus_import":"1","publication_identifier":{"eisbn":["9781119860914"]},"article_processing_charge":"No","day":"08","month":"08","publisher":"Wiley","editor":[{"full_name":"Huttner, Wieland","first_name":"Wieland","last_name":"Huttner"}],"department":[{"_id":"SiHi"}],"publication_status":"published","title":"Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression","status":"public","year":"2023","_id":"14757","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"None","date_updated":"2024-01-09T09:46:57Z","date_created":"2024-01-08T13:16:36Z","author":[{"full_name":"Villalba Requena, Ana","id":"68cb85a0-39f7-11eb-9559-9aaab4f6a247","orcid":"0000-0002-5615-5277","first_name":"Ana","last_name":"Villalba Requena"},{"orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","first_name":"Nicole","full_name":"Amberg, Nicole"},{"last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"type":"book_chapter","abstract":[{"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.","lang":"eng"}]},{"doi":"10.3390/cells12081133","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["37190042"],"isi":["000977445700001"]},"isi":1,"quality_controlled":"1","publication_identifier":{"issn":["2073-4409"]},"month":"04","author":[{"full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87","last_name":"Cheung","first_name":"Giselle T"},{"last_name":"Chever","first_name":"Oana","full_name":"Chever, Oana"},{"first_name":"Astrid","last_name":"Rollenhagen","full_name":"Rollenhagen, Astrid"},{"full_name":"Quenech’du, Nicole","last_name":"Quenech’du","first_name":"Nicole"},{"full_name":"Ezan, Pascal","first_name":"Pascal","last_name":"Ezan"},{"first_name":"Joachim H. R.","last_name":"Lübke","full_name":"Lübke, Joachim H. R."},{"last_name":"Rouach","first_name":"Nathalie","full_name":"Rouach, Nathalie"}],"volume":12,"date_created":"2024-01-10T09:46:35Z","date_updated":"2024-01-16T09:29:35Z","pmid":1,"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.","year":"2023","department":[{"_id":"SiHi"}],"publisher":"MDPI","publication_status":"published","file_date_updated":"2024-01-16T09:26:52Z","article_number":"1133","date_published":"2023-04-11T00:00:00Z","citation":{"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.","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).","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.","ieee":"G. T. Cheung et al., “Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses,” Cells, vol. 12, no. 8. MDPI, 2023.","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","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"},"publication":"Cells","article_type":"original","article_processing_charge":"Yes","has_accepted_license":"1","day":"11","keyword":["General Medicine"],"oa_version":"Published Version","file":[{"relation":"main_file","file_id":"14808","date_created":"2024-01-16T09:26:52Z","date_updated":"2024-01-16T09:26:52Z","checksum":"6798cd75d8857976fbc58a43fd173d68","success":1,"file_name":"2023_Cells_Cheung.pdf","access_level":"open_access","file_size":7931643,"content_type":"application/pdf","creator":"dernst"}],"_id":"14783","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 12","ddc":["570"],"title":"Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses","status":"public","issue":"8","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."}],"type":"journal_article"},{"month":"04","publication_identifier":{"issn":["0092-8674"]},"quality_controlled":"1","isi":1,"project":[{"call_identifier":"FWF","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000991468700001"]},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.cell.2023.02.037","file_date_updated":"2023-05-02T09:26:21Z","ec_funded":1,"publication_status":"published","publisher":"Elsevier","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"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.","year":"2023","date_created":"2023-04-05T08:15:40Z","date_updated":"2024-02-07T08:03:32Z","volume":186,"author":[{"full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","last_name":"Knaus"},{"orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette"},{"full_name":"Malzl, Daniel","first_name":"Daniel","last_name":"Malzl"},{"full_name":"Gerykova Bujalkova, Maria","last_name":"Gerykova Bujalkova","first_name":"Maria"},{"last_name":"Smogavec","first_name":"Mateja","full_name":"Smogavec, Mateja"},{"full_name":"Schwarz, Lena A.","first_name":"Lena A.","last_name":"Schwarz"},{"id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","last_name":"Gorkiewicz","first_name":"Sarah","full_name":"Gorkiewicz, Sarah"},{"full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg"},{"full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian"},{"last_name":"Knittl-Frank","first_name":"Christian","full_name":"Knittl-Frank, Christian"},{"full_name":"Tassinari, Marianna","id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e","last_name":"Tassinari","first_name":"Marianna"},{"full_name":"Maulide, Nuno","last_name":"Maulide","first_name":"Nuno"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"last_name":"Menche","first_name":"Jörg","full_name":"Menche, Jörg"},{"full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"related_material":{"record":[{"id":"13107","status":"public","relation":"dissertation_contains"}],"link":[{"url":"https://ista.ac.at/en/news/feed-them-or-lose-them/","relation":"press_release","description":"News on ISTA Website"}]},"keyword":["General Biochemistry","Genetics and Molecular Biology"],"scopus_import":"1","day":"27","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","article_type":"original","page":"1950-1967.e25","publication":"Cell","citation":{"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.","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.","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.","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","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.","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","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."},"date_published":"2023-04-27T00:00:00Z","type":"journal_article","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."}],"issue":"9","status":"public","title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","ddc":["570"],"intvolume":" 186","_id":"12802","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"access_level":"open_access","file_name":"2023_Cell_Knaus.pdf","creator":"dernst","content_type":"application/pdf","file_size":15712841,"file_id":"12889","relation":"main_file","success":1,"checksum":"47e94fbe19e86505b429cb7a5b503ce6","date_created":"2023-05-02T09:26:21Z","date_updated":"2023-05-02T09:26:21Z"}],"oa_version":"Published Version"}]