--- _id: '7253' abstract: - lang: eng text: The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor cell and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype. acknowledged_ssus: - _id: PreCl article_number: '195' article_processing_charge: No article_type: original author: - first_name: Susanne full_name: Laukoter, Susanne id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87 last_name: Laukoter orcid: 0000-0002-7903-3010 - first_name: Robert J full_name: Beattie, Robert J id: 2E26DF60-F248-11E8-B48F-1D18A9856A87 last_name: Beattie orcid: 0000-0002-8483-8753 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Keiichi I. full_name: Nakayama, Keiichi I. last_name: Nakayama - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 2020;11. doi:10.1038/s41467-019-14077-2 apa: Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., & Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-14077-2 chicago: Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-019-14077-2. ieee: S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer, “Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development,” Nature Communications, vol. 11. Springer Nature, 2020. ista: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. 2020. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 11, 195. mla: Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications, vol. 11, 195, Springer Nature, 2020, doi:10.1038/s41467-019-14077-2. short: S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer, Nature Communications 11 (2020). date_created: 2020-01-11T10:42:48Z date_published: 2020-01-10T00:00:00Z date_updated: 2023-08-17T14:23:41Z day: '10' ddc: - '570' department: - _id: SiHi doi: 10.1038/s41467-019-14077-2 ec_funded: 1 external_id: isi: - '000551459000005' file: - access_level: open_access checksum: ebf1ed522f4e0be8d94c939c1806a709 content_type: application/pdf creator: dernst date_created: 2020-01-13T07:42:31Z date_updated: 2020-07-14T12:47:54Z file_id: '7261' file_name: 2020_NatureComm_Laukoter.pdf file_size: 8063333 relation: main_file file_date_updated: 2020-07-14T12:47:54Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '01' oa: 1 oa_version: Published Version project: - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _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: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/ scopus_import: '1' status: public title: Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development 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: 11 year: '2020' ... --- _id: '7593' abstract: - lang: eng text: Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from Pafah1b1-deficient mutants. Pafah1b1-deficient neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with mislocalization of furrow-associated markers, associated with actomyosin dysfunction and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility is tightly controlled to execute proper daughter cell separation. article_number: '51512' article_processing_charge: No article_type: original author: - first_name: Hyang Mi full_name: Moon, Hyang Mi last_name: Moon - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Liqun full_name: Luo, Liqun last_name: Luo - first_name: Anthony full_name: Wynshaw-Boris, Anthony last_name: Wynshaw-Boris citation: ama: Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. eLife. 2020;9. doi:10.7554/elife.51512 apa: Moon, H. M., Hippenmeyer, S., Luo, L., & Wynshaw-Boris, A. (2020). LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.51512 chicago: Moon, Hyang Mi, Simon Hippenmeyer, Liqun Luo, and Anthony Wynshaw-Boris. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.51512. ieee: H. M. Moon, S. Hippenmeyer, L. Luo, and A. Wynshaw-Boris, “LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. 2020. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. eLife. 9, 51512. mla: Moon, Hyang Mi, et al. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” ELife, vol. 9, 51512, eLife Sciences Publications, 2020, doi:10.7554/elife.51512. short: H.M. Moon, S. Hippenmeyer, L. Luo, A. Wynshaw-Boris, ELife 9 (2020). date_created: 2020-03-20T13:16:41Z date_published: 2020-03-11T00:00:00Z date_updated: 2023-08-18T07:06:31Z day: '11' ddc: - '570' department: - _id: SiHi doi: 10.7554/elife.51512 external_id: isi: - '000522835800001' pmid: - '32159512' file: - access_level: open_access checksum: 396ceb2dd10b102ef4e699666b9342c3 content_type: application/pdf creator: dernst date_created: 2020-09-24T07:03:20Z date_updated: 2020-09-24T07:03:20Z file_id: '8567' file_name: 2020_elife_Moon.pdf file_size: 15089438 relation: main_file success: 1 file_date_updated: 2020-09-24T07:03:20Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/751958 month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility 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: 9 year: '2020' ... --- _id: '8093' abstract: - lang: eng text: "Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.\r\nMethods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.\r\nResults: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.\r\nConclusion: We propose that the chemokine axis CCL20–CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy." acknowledgement: "The authors would like to thank A. van Lierop for technical assistance. In addition, we thank C. Dullin, J. Missbach-Güntner and S. Greco for advice and assistance with fpVCT imaging. Furthermore, the authors would like to thank H. K. Horst for advice on performing matrigel plug assays. This study has also been partially presented in A. Schorr’s doctoral thesis and the funding report of the SPP 1190 ‘The tumor-vessel interface’ of the ‘Deutsche Forschungsgemeinschaft’ (DFG).\r\nThis project was funded by the SPP 1190 “The tumor-vessel interface” and HO 2092/8-1 of the ‘Deutsche Forschungsgemeinschaft’ (DFG) to B. Homey. In addition, it was supported by grants from the Austrian Science Fund (FWF, W1212 to N. Amberg and J. Klufa and I4300-B to T. Bauer), the WWTF project LS16-025 and the European Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883) to M. Sibilia." article_processing_charge: No article_type: original author: - first_name: Andreas full_name: Hippe, Andreas last_name: Hippe - first_name: Stephan Alexander full_name: Braun, Stephan Alexander last_name: Braun - first_name: Péter full_name: Oláh, Péter last_name: Oláh - first_name: Peter Arne full_name: Gerber, Peter Arne last_name: Gerber - first_name: Anne full_name: Schorr, Anne last_name: Schorr - first_name: Stephan full_name: Seeliger, Stephan last_name: Seeliger - first_name: Stephanie full_name: Holtz, Stephanie last_name: Holtz - first_name: Katharina full_name: Jannasch, Katharina last_name: Jannasch - first_name: Andor full_name: Pivarcsi, Andor last_name: Pivarcsi - first_name: Bettina full_name: Buhren, Bettina last_name: Buhren - first_name: Holger full_name: Schrumpf, Holger last_name: Schrumpf - first_name: Andreas full_name: Kislat, Andreas last_name: Kislat - first_name: Erich full_name: Bünemann, Erich last_name: Bünemann - first_name: Martin full_name: Steinhoff, Martin last_name: Steinhoff - first_name: Jens full_name: Fischer, Jens last_name: Fischer - first_name: Sérgio A. full_name: Lira, Sérgio A. last_name: Lira - first_name: Petra full_name: Boukamp, Petra last_name: Boukamp - first_name: Peter full_name: Hevezi, Peter last_name: Hevezi - first_name: Nikolas Hendrik full_name: Stoecklein, Nikolas Hendrik last_name: Stoecklein - first_name: Thomas full_name: Hoffmann, Thomas last_name: Hoffmann - first_name: Frauke full_name: Alves, Frauke last_name: Alves - first_name: Jonathan full_name: Sleeman, Jonathan last_name: Sleeman - first_name: Thomas full_name: Bauer, Thomas last_name: Bauer - first_name: Jörg full_name: Klufa, Jörg last_name: Klufa - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Maria full_name: Sibilia, Maria last_name: Sibilia - first_name: Albert full_name: Zlotnik, Albert last_name: Zlotnik - first_name: Anja full_name: Müller-Homey, Anja last_name: Müller-Homey - first_name: Bernhard full_name: Homey, Bernhard last_name: Homey citation: ama: Hippe A, Braun SA, Oláh P, et al. EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British Journal of Cancer. 2020;123:942-954. doi:10.1038/s41416-020-0943-2 apa: Hippe, A., Braun, S. A., Oláh, P., Gerber, P. A., Schorr, A., Seeliger, S., … Homey, B. (2020). EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British Journal of Cancer. Springer Nature. https://doi.org/10.1038/s41416-020-0943-2 chicago: Hippe, Andreas, Stephan Alexander Braun, Péter Oláh, Peter Arne Gerber, Anne Schorr, Stephan Seeliger, Stephanie Holtz, et al. “EGFR/Ras-Induced CCL20 Production Modulates the Tumour Microenvironment.” British Journal of Cancer. Springer Nature, 2020. https://doi.org/10.1038/s41416-020-0943-2. ieee: A. Hippe et al., “EGFR/Ras-induced CCL20 production modulates the tumour microenvironment,” British Journal of Cancer, vol. 123. Springer Nature, pp. 942–954, 2020. ista: Hippe A, Braun SA, Oláh P, Gerber PA, Schorr A, Seeliger S, Holtz S, Jannasch K, Pivarcsi A, Buhren B, Schrumpf H, Kislat A, Bünemann E, Steinhoff M, Fischer J, Lira SA, Boukamp P, Hevezi P, Stoecklein NH, Hoffmann T, Alves F, Sleeman J, Bauer T, Klufa J, Amberg N, Sibilia M, Zlotnik A, Müller-Homey A, Homey B. 2020. EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British Journal of Cancer. 123, 942–954. mla: Hippe, Andreas, et al. “EGFR/Ras-Induced CCL20 Production Modulates the Tumour Microenvironment.” British Journal of Cancer, vol. 123, Springer Nature, 2020, pp. 942–54, doi:10.1038/s41416-020-0943-2. short: A. Hippe, S.A. Braun, P. Oláh, P.A. Gerber, A. Schorr, S. Seeliger, S. Holtz, K. Jannasch, A. Pivarcsi, B. Buhren, H. Schrumpf, A. Kislat, E. Bünemann, M. Steinhoff, J. Fischer, S.A. Lira, P. Boukamp, P. Hevezi, N.H. Stoecklein, T. Hoffmann, F. Alves, J. Sleeman, T. Bauer, J. Klufa, N. Amberg, M. Sibilia, A. Zlotnik, A. Müller-Homey, B. Homey, British Journal of Cancer 123 (2020) 942–954. date_created: 2020-07-05T22:00:46Z date_published: 2020-09-15T00:00:00Z date_updated: 2023-08-22T07:51:12Z day: '15' ddc: - '610' department: - _id: SiHi doi: 10.1038/s41416-020-0943-2 external_id: isi: - '000544152500001' pmid: - '32601464' file: - access_level: open_access checksum: 05a8e65d49c3f5b8e37ac4afe68287e2 content_type: application/pdf creator: cchlebak date_created: 2021-12-02T12:35:12Z date_updated: 2021-12-02T12:35:12Z file_id: '10398' file_name: 2020_BrJournalCancer_Hippe.pdf file_size: 3620691 relation: main_file success: 1 file_date_updated: 2021-12-02T12:35:12Z has_accepted_license: '1' intvolume: ' 123' isi: 1 language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: 942-954 pmid: 1 publication: British Journal of Cancer publication_identifier: eissn: - 1532-1827 issn: - 0007-0920 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: erratum url: https://doi.org/10.1038/s41416-021-01563-y record: - id: '10170' relation: later_version status: deleted scopus_import: '1' status: public title: EGFR/Ras-induced CCL20 production modulates the tumour microenvironment 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: 123 year: '2020' ... --- _id: '8162' abstract: - lang: eng text: In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo for comments on earlier versions of the manuscript. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031). R.B. received support from the FWF Meitner-Programm (M 2416). This work was also supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement 618444 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H. article_processing_charge: No article_type: original author: - first_name: Susanne full_name: Laukoter, Susanne id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87 last_name: Laukoter orcid: 0000-0002-7903-3010 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Robert J full_name: Beattie, Robert J id: 2E26DF60-F248-11E8-B48F-1D18A9856A87 last_name: Beattie orcid: 0000-0002-8483-8753 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Thomas full_name: Penz, Thomas last_name: Penz - first_name: Christoph full_name: Bock, Christoph last_name: Bock orcid: 0000-0001-6091-3088 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 2020;107(6):1160-1179.e9. doi:10.1016/j.neuron.2020.06.031 apa: Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher, C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.06.031 chicago: Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.06.031. ieee: S. Laukoter et al., “Cell-type specificity of genomic imprinting in cerebral cortex,” Neuron, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020. ista: Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T, Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 107(6), 1160–1179.e9. mla: Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:10.1016/j.neuron.2020.06.031. short: S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher, T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9. date_created: 2020-07-23T16:03:12Z date_published: 2020-09-23T00:00:00Z date_updated: 2023-08-22T08:20:11Z day: '23' ddc: - '570' department: - _id: SiHi doi: 10.1016/j.neuron.2020.06.031 ec_funded: 1 external_id: isi: - '000579698700006' file: - access_level: open_access checksum: 7becdc16a6317304304631087ae7dd7f content_type: application/pdf creator: dernst date_created: 2020-12-02T09:26:46Z date_updated: 2020-12-02T09:26:46Z file_id: '8828' file_name: 2020_Neuron_Laukoter.pdf file_size: 8911830 relation: main_file success: 1 file_date_updated: 2020-12-02T09:26:46Z has_accepted_license: '1' intvolume: ' 107' isi: 1 issue: '6' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '09' oa: 1 oa_version: Published Version page: 1160-1179.e9 project: - _id: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _id: 25D92700-B435-11E9-9278-68D0E5697425 grant_number: LS13-002 name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain - _id: 25D7962E-B435-11E9-9278-68D0E5697425 grant_number: RGP0053/2014 name: Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level - _id: 25D61E48-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618444' name: Molecular Mechanisms of Cerebral Cortex Development - _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: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Website relation: press_release url: https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/ scopus_import: '1' status: public title: Cell-type specificity of genomic imprinting in cerebral cortex tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 107 year: '2020' ... --- _id: '8592' abstract: - lang: eng text: Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma. acknowledgement: The authors thank Drs. J. Eisen, QR. Lu, S. Duan, Z‐H. Li, W. Mo, and Q. Wu for their critical comments on the manuscript. They also thank Dr. H. Zong for providing the CKO_NG2‐CreER model. This work is supported by the National Key Research and Development Program of China, Stem Cell and Translational Research (2016YFA0101201 to C.L., 2016YFA0100303 to Y.J.W.), the National Natural Science Foundation of China (81673035 and 81972915 to C.L., 81472722 to Y.J.W.), the Science Foundation for Distinguished Young Scientists of Zhejiang Province (LR17H160001 to C.L.), Fundamental Research Funds for the Central Universities (2016QNA7023 and 2017QNA7028 to C.L.) and the Thousand Talent Program for Young Outstanding Scientists, China (to C.L.), IST Austria institutional funds (to S.H.), European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (725780 LinPro to S.H.). C.L. is a scholar of K. C. Wong Education Foundation. article_number: '2001724' article_processing_charge: No article_type: original author: - first_name: Anhao full_name: Tian, Anhao last_name: Tian - first_name: Bo full_name: Kang, Bo last_name: Kang - first_name: Baizhou full_name: Li, Baizhou last_name: Li - first_name: Biying full_name: Qiu, Biying last_name: Qiu - first_name: Wenhong full_name: Jiang, Wenhong last_name: Jiang - first_name: Fangjie full_name: Shao, Fangjie last_name: Shao - first_name: Qingqing full_name: Gao, Qingqing last_name: Gao - first_name: Rui full_name: Liu, Rui last_name: Liu - first_name: Chengwei full_name: Cai, Chengwei last_name: Cai - first_name: Rui full_name: Jing, Rui last_name: Jing - first_name: Wei full_name: Wang, Wei last_name: Wang - first_name: Pengxiang full_name: Chen, Pengxiang last_name: Chen - first_name: Qinghui full_name: Liang, Qinghui last_name: Liang - first_name: Lili full_name: Bao, Lili last_name: Bao - first_name: Jianghong full_name: Man, Jianghong last_name: Man - first_name: Yan full_name: Wang, Yan last_name: Wang - first_name: Yu full_name: Shi, Yu last_name: Shi - first_name: Jin full_name: Li, Jin last_name: Li - first_name: Minmin full_name: Yang, Minmin last_name: Yang - first_name: Lisha full_name: Wang, Lisha last_name: Wang - first_name: Jianmin full_name: Zhang, Jianmin last_name: Zhang - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Junming full_name: Zhu, Junming last_name: Zhu - first_name: Xiuwu full_name: Bian, Xiuwu last_name: Bian - first_name: Ying‐Jie full_name: Wang, Ying‐Jie last_name: Wang - first_name: Chong full_name: Liu, Chong last_name: Liu citation: ama: Tian A, Kang B, Li B, et al. Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. Advanced Science. 2020;7(21). doi:10.1002/advs.202001724 apa: Tian, A., Kang, B., Li, B., Qiu, B., Jiang, W., Shao, F., … Liu, C. (2020). Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. Advanced Science. Wiley. https://doi.org/10.1002/advs.202001724 chicago: Tian, Anhao, Bo Kang, Baizhou Li, Biying Qiu, Wenhong Jiang, Fangjie Shao, Qingqing Gao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.” Advanced Science. Wiley, 2020. https://doi.org/10.1002/advs.202001724. ieee: A. Tian et al., “Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting,” Advanced Science, vol. 7, no. 21. Wiley, 2020. ista: Tian A, Kang B, Li B, Qiu B, Jiang W, Shao F, Gao Q, Liu R, Cai C, Jing R, Wang W, Chen P, Liang Q, Bao L, Man J, Wang Y, Shi Y, Li J, Yang M, Wang L, Zhang J, Hippenmeyer S, Zhu J, Bian X, Wang Y, Liu C. 2020. Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. Advanced Science. 7(21), 2001724. mla: Tian, Anhao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.” Advanced Science, vol. 7, no. 21, 2001724, Wiley, 2020, doi:10.1002/advs.202001724. short: A. Tian, B. Kang, B. Li, B. Qiu, W. Jiang, F. Shao, Q. Gao, R. Liu, C. Cai, R. Jing, W. Wang, P. Chen, Q. Liang, L. Bao, J. Man, Y. Wang, Y. Shi, J. Li, M. Yang, L. Wang, J. Zhang, S. Hippenmeyer, J. Zhu, X. Bian, Y. Wang, C. Liu, Advanced Science 7 (2020). date_created: 2020-10-01T09:44:13Z date_published: 2020-11-04T00:00:00Z date_updated: 2023-08-22T09:53:01Z day: '04' ddc: - '570' department: - _id: SiHi doi: 10.1002/advs.202001724 ec_funded: 1 external_id: isi: - '000573860700001' file: - access_level: open_access checksum: 92818c23ecc70e35acfa671f3cfb9909 content_type: application/pdf creator: dernst date_created: 2020-12-10T14:07:24Z date_updated: 2020-12-10T14:07:24Z file_id: '8938' file_name: 2020_AdvScience_Tian.pdf file_size: 7835833 relation: main_file success: 1 file_date_updated: 2020-12-10T14:07:24Z has_accepted_license: '1' intvolume: ' 7' isi: 1 issue: '21' keyword: - General Engineering - General Physics and Astronomy - General Materials Science - Medicine (miscellaneous) - General Chemical Engineering - Biochemistry - Genetics and Molecular Biology (miscellaneous) 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 publication: Advanced Science publication_identifier: issn: - 2198-3844 publication_status: published publisher: Wiley quality_controlled: '1' status: public title: Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting 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: 7 year: '2020' ... --- _id: '8949' abstract: - lang: eng text: Development of the nervous system undergoes important transitions, including one from neurogenesis to gliogenesis which occurs late during embryonic gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic Analysis with Double Markers (MADM) with quantitative and computational methods. Results reveal that developmental gliogenesis in the cerebral cortex occurs in a fraction of earlier neurogenic clones, accelerating around E16.5, and giving rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices. A broad range in the proliferation capacity, symmetry of clones, and competitive advantage of MADM cells was evident in clones that contained one cellular lineage with double dosage of Egfr relative to their environment, while their sibling Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia in MADM clones balance out regardless of significant alterations in clonal symmetries. The variability in glial clones shows stochastic patterns that we define mathematically, which are different from the deterministic patterns in neuronal clones. This study sets a foundation for studying the biological significance of stochastic and deterministic clonal principles underlying tissue development, and identifying mechanisms that differentiate between neurogenesis and gliogenesis. acknowledgement: This research was funded by grants from the National Institutes of Health to H.T.G. (R01NS098370 and R01NS089795). C.V.M. was supported by a National Science Foundation Graduate Research Fellowship (DGE-1746939). R.B. was supported by the FWF Lise-Meitner program (M 2416), and S.H. was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 725780 LinPro).The authors thank members of the Ghashghaei lab for discussions, technical support, and help with preparation of the manuscript. article_number: '2662' article_processing_charge: No article_type: original author: - first_name: Xuying full_name: Zhang, Xuying last_name: Zhang - first_name: Christine V. full_name: Mennicke, Christine V. last_name: Mennicke - first_name: Guanxi full_name: Xiao, Guanxi last_name: Xiao - first_name: Robert J full_name: Beattie, Robert J id: 2E26DF60-F248-11E8-B48F-1D18A9856A87 last_name: Beattie orcid: 0000-0002-8483-8753 - first_name: Mansoor full_name: Haider, Mansoor last_name: Haider - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: H. Troy full_name: Ghashghaei, H. Troy last_name: Ghashghaei citation: ama: Zhang X, Mennicke CV, Xiao G, et al. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. 2020;9(12). doi:10.3390/cells9122662 apa: Zhang, X., Mennicke, C. V., Xiao, G., Beattie, R. J., Haider, M., Hippenmeyer, S., & Ghashghaei, H. T. (2020). Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. MDPI. https://doi.org/10.3390/cells9122662 chicago: Zhang, Xuying, Christine V. Mennicke, Guanxi Xiao, Robert J Beattie, Mansoor Haider, Simon Hippenmeyer, and H. Troy Ghashghaei. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” Cells. MDPI, 2020. https://doi.org/10.3390/cells9122662. ieee: X. Zhang et al., “Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage,” Cells, vol. 9, no. 12. MDPI, 2020. ista: Zhang X, Mennicke CV, Xiao G, Beattie RJ, Haider M, Hippenmeyer S, Ghashghaei HT. 2020. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. 9(12), 2662. mla: Zhang, Xuying, et al. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” Cells, vol. 9, no. 12, 2662, MDPI, 2020, doi:10.3390/cells9122662. short: X. Zhang, C.V. Mennicke, G. Xiao, R.J. Beattie, M. Haider, S. Hippenmeyer, H.T. Ghashghaei, Cells 9 (2020). date_created: 2020-12-14T08:04:03Z date_published: 2020-12-11T00:00:00Z date_updated: 2023-08-24T10:57:48Z day: '11' ddc: - '570' department: - _id: SiHi doi: 10.3390/cells9122662 ec_funded: 1 external_id: isi: - '000601787300001' file: - access_level: open_access checksum: 5095cbdc728c9a510c5761cf60a8861c content_type: application/pdf creator: dernst date_created: 2020-12-14T08:09:43Z date_updated: 2020-12-14T08:09:43Z file_id: '8950' file_name: 2020_Cells_Zhang.pdf file_size: 3504525 relation: main_file success: 1 file_date_updated: 2020-12-14T08:09:43Z has_accepted_license: '1' intvolume: ' 9' isi: 1 issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Published Version project: - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _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: Cells publication_identifier: issn: - 2073-4409 publication_status: published publisher: MDPI quality_controlled: '1' status: public title: Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage 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: 9 year: '2020' ... --- _id: '8813' abstract: - lang: eng text: 'In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation.' article_processing_charge: No author: - first_name: Laura full_name: Santini, Laura last_name: Santini - first_name: Florian full_name: Halbritter, Florian last_name: Halbritter - first_name: Fabian full_name: Titz-Teixeira, Fabian last_name: Titz-Teixeira - first_name: Toru full_name: Suzuki, Toru last_name: Suzuki - first_name: Maki full_name: Asami, Maki last_name: Asami - first_name: Julia full_name: Ramesmayer, Julia last_name: Ramesmayer - first_name: Xiaoyan full_name: Ma, Xiaoyan last_name: Ma - first_name: Andreas full_name: Lackner, Andreas last_name: Lackner - first_name: Nick full_name: Warr, Nick last_name: Warr - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Ernest full_name: Laue, Ernest last_name: Laue - first_name: Matthias full_name: Farlik, Matthias last_name: Farlik - first_name: Christoph full_name: Bock, Christoph last_name: Bock - first_name: Andreas full_name: Beyer, Andreas last_name: Beyer - first_name: Anthony C. F. full_name: Perry, Anthony C. F. last_name: Perry - first_name: Martin full_name: Leeb, Martin last_name: Leeb citation: ama: Santini L, Halbritter F, Titz-Teixeira F, et al. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. bioRxiv. doi:10.1101/2020.11.03.366948 apa: Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ramesmayer, J., … Leeb, M. (n.d.). Novel imprints in mouse blastocysts are predominantly DNA methylation independent. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.11.03.366948 chicago: Santini, Laura, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki, Maki Asami, Julia Ramesmayer, Xiaoyan Ma, et al. “Novel Imprints in Mouse Blastocysts Are Predominantly DNA Methylation Independent.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.11.03.366948. ieee: L. Santini et al., “Novel imprints in mouse blastocysts are predominantly DNA methylation independent,” bioRxiv. Cold Spring Harbor Laboratory. ista: Santini L, Halbritter F, Titz-Teixeira F, Suzuki T, Asami M, Ramesmayer J, Ma X, Lackner A, Warr N, Pauler F, Hippenmeyer S, Laue E, Farlik M, Bock C, Beyer A, Perry ACF, Leeb M. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. bioRxiv, 10.1101/2020.11.03.366948. mla: Santini, Laura, et al. “Novel Imprints in Mouse Blastocysts Are Predominantly DNA Methylation Independent.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.11.03.366948. short: L. Santini, F. Halbritter, F. Titz-Teixeira, T. Suzuki, M. Asami, J. Ramesmayer, X. Ma, A. Lackner, N. Warr, F. Pauler, S. Hippenmeyer, E. Laue, M. Farlik, C. Bock, A. Beyer, A.C.F. Perry, M. Leeb, BioRxiv (n.d.). date_created: 2020-11-26T07:17:19Z date_published: 2020-11-05T00:00:00Z date_updated: 2023-09-12T11:05:28Z day: '05' department: - _id: SiHi doi: 10.1101/2020.11.03.366948 external_id: pmid: - 'PPR234457 ' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.11.03.366948 month: '11' oa: 1 oa_version: Preprint pmid: 1 publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory status: public title: Novel imprints in mouse blastocysts are predominantly DNA methylation independent type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8569' abstract: - lang: eng text: Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration in vivo are however still unclear, let alone the effects and interactions with the extracellular environment. In any in vivo context, cells will always be exposed to a complex extracellular environment consisting of (1) secreted factors acting as potential signaling cues, (2) the extracellular matrix, and (3) other cells providing cell–cell interaction through receptors and/or direct physical stimuli. Most studies so far have described and focused mainly on intrinsic cell-autonomous gene functions in neuronal migration but there is accumulating evidence that non-cell-autonomous-, local-, systemic-, and/or whole tissue-wide effects substantially contribute to the regulation of radial neuronal migration. These non-cell-autonomous effects may differentially affect cortical neuron migration in distinct cellular environments. However, the cellular and molecular natures of such non-cell-autonomous mechanisms are mostly unknown. Furthermore, physical forces due to collective migration and/or community effects (i.e., interactions with surrounding cells) may play important roles in neocortical projection neuron migration. In this concise review, we first outline distinct models of non-cell-autonomous interactions of cortical projection neurons along their radial migration trajectory during development. We then summarize experimental assays and platforms that can be utilized to visualize and potentially probe non-cell-autonomous mechanisms. Lastly, we define key questions to address in the future. acknowledgement: AH 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 SH. article_number: '574382' article_processing_charge: Yes (via OA deal) article_type: original 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. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. 2020;8(9). doi:10.3389/fcell.2020.574382 apa: Hansen, A. H., & Hippenmeyer, S. (2020). Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. Frontiers. https://doi.org/10.3389/fcell.2020.574382 chicago: Hansen, Andi H, and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” Frontiers in Cell and Developmental Biology. Frontiers, 2020. https://doi.org/10.3389/fcell.2020.574382. ieee: A. H. Hansen and S. Hippenmeyer, “Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex,” Frontiers in Cell and Developmental Biology, vol. 8, no. 9. Frontiers, 2020. ista: Hansen AH, Hippenmeyer S. 2020. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. 8(9), 574382. mla: Hansen, Andi H., and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” Frontiers in Cell and Developmental Biology, vol. 8, no. 9, 574382, Frontiers, 2020, doi:10.3389/fcell.2020.574382. short: A.H. Hansen, S. Hippenmeyer, Frontiers in Cell and Developmental Biology 8 (2020). date_created: 2020-09-26T06:11:07Z date_published: 2020-09-25T00:00:00Z date_updated: 2024-03-27T23:30:40Z day: '25' ddc: - '570' department: - _id: SiHi doi: 10.3389/fcell.2020.574382 ec_funded: 1 external_id: isi: - '000577915900001' pmid: - '33102480' file: - access_level: open_access checksum: 01f731824194c94c81a5da360d997073 content_type: application/pdf creator: dernst date_created: 2020-09-28T13:11:17Z date_updated: 2020-09-28T13:11:17Z file_id: '8584' file_name: 2020_Frontiers_Hansen.pdf file_size: 5527139 relation: main_file success: 1 file_date_updated: 2020-09-28T13:11:17Z has_accepted_license: '1' intvolume: ' 8' isi: 1 issue: '9' language: - iso: eng month: '09' 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 - _id: 25D61E48-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618444' name: Molecular Mechanisms of Cerebral Cortex Development publication: Frontiers in Cell and Developmental Biology publication_identifier: issn: - 2296-634X publication_status: published publisher: Frontiers quality_controlled: '1' related_material: record: - id: '9962' relation: dissertation_contains status: public scopus_import: '1' status: public title: Non-cell-autonomous mechanisms in radial projection neuron migration in the 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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 8 year: '2020' ... --- _id: '7815' abstract: - lang: eng text: Beginning from a limited pool of progenitors, the mammalian cerebral cortex forms highly organized functional neural circuits. However, the underlying cellular and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs) and eventual production of neurons and glia in the developing neuroepithelium remains unclear. Methods to trace NSC division patterns and map the lineage of clonally related cells have advanced dramatically. However, many contemporary lineage tracing techniques suffer from the lack of cellular resolution of progeny cell fate, which is essential for deciphering progenitor cell division patterns. Presented is a protocol using mosaic analysis with double markers (MADM) to perform in vivo clonal analysis. MADM concomitantly manipulates individual progenitor cells and visualizes precise division patterns and lineage progression at unprecedented single cell resolution. MADM-based interchromosomal recombination events during the G2-X phase of mitosis, together with temporally inducible CreERT2, provide exact information on the birth dates of clones and their division patterns. Thus, MADM lineage tracing provides unprecedented qualitative and quantitative optical readouts of the proliferation mode of stem cell progenitors at the single cell level. MADM also allows for examination of the mechanisms and functional requirements of candidate genes in NSC lineage progression. This method is unique in that comparative analysis of control and mutant subclones can be performed in the same tissue environment in vivo. Here, the protocol is described in detail, and experimental paradigms to employ MADM for clonal analysis and lineage tracing in the developing cerebral cortex are demonstrated. Importantly, this protocol can be adapted to perform MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver is present. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl article_number: e61147 article_processing_charge: No article_type: original author: - first_name: Robert J full_name: Beattie, Robert J id: 2E26DF60-F248-11E8-B48F-1D18A9856A87 last_name: Beattie orcid: 0000-0002-8483-8753 - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - 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: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - 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: Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. 2020;(159). doi:10.3791/61147 apa: Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen, A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147 chicago: Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal of Visual Experiments. MyJove Corporation, 2020. https://doi.org/10.3791/61147. ieee: R. J. Beattie et al., “Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM),” Journal of Visual Experiments, no. 159. MyJove Corporation, 2020. ista: Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159), e61147. mla: Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal of Visual Experiments, no. 159, e61147, MyJove Corporation, 2020, doi:10.3791/61147. short: R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen, S. Hippenmeyer, Journal of Visual Experiments (2020). date_created: 2020-05-11T08:31:20Z date_published: 2020-05-08T00:00:00Z date_updated: 2024-03-27T23:30:41Z day: '08' ddc: - '570' department: - _id: SiHi doi: 10.3791/61147 ec_funded: 1 external_id: isi: - '000546406600043' file: - access_level: open_access checksum: 3154ea7f90b9fb45e084cd1c2770597d content_type: application/pdf creator: rbeattie date_created: 2020-05-11T08:28:38Z date_updated: 2020-07-14T12:48:03Z file_id: '7816' file_name: jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf file_size: 1352186 relation: main_file file_date_updated: 2020-07-14T12:48:03Z has_accepted_license: '1' isi: 1 issue: '159' language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _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: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration - _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: Journal of Visual Experiments publication_identifier: issn: - 1940-087X publication_status: published publisher: MyJove Corporation quality_controlled: '1' related_material: record: - id: '7902' relation: part_of_dissertation status: public scopus_import: '1' status: public title: Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM) 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 year: '2020' ... --- _id: '7902' abstract: - lang: eng text: "Mosaic genetic analysis has been widely used in different model organisms such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific fashion. More recently, and less easily conducted, mosaic genetic analysis in mice has also been enabled with the ambition to shed light on human gene function and disease. These genetic tools are of particular interest, but not restricted to, the study of the brain. Notably, the MADM technology offers a genetic approach in mice to visualize and concomitantly manipulate small subsets of genetically defined cells at a clonal level and single cell resolution. MADM-based analysis has already advanced the study of genetic mechanisms regulating brain development and is expected that further MADM-based analysis of genetic alterations will continue to reveal important insights on the fundamental principles of development and disease to potentially assist in the development of new therapies or treatments.\r\nIn summary, this work completed and characterized the necessary genome-wide genetic tools to perform MADM-based analysis at single cell level of the vast majority of mouse genes in virtually any cell type and provided a protocol to perform lineage tracing using the novel MADM resource. Importantly, this work also explored and revealed novel aspects of biologically relevant events in an in vivo context, such as the chromosome-specific bias of chromatid sister segregation pattern, the generation of cell-type diversity in the cerebral cortex and in the cerebellum and finally, the relevance of the interplay between the cell-autonomous gene function and cell-non-autonomous (community) effects in radial glial progenitor lineage progression.\r\nThis work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation." acknowledged_ssus: - _id: PreCl - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras citation: ama: Contreras X. Genetic dissection of neural development in health and disease at single cell resolution. 2020. doi:10.15479/AT:ISTA:7902 apa: Contreras, X. (2020). Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7902 chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7902. ieee: X. Contreras, “Genetic dissection of neural development in health and disease at single cell resolution,” Institute of Science and Technology Austria, 2020. ista: Contreras X. 2020. Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria. mla: Contreras, Ximena. Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7902. short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution, Institute of Science and Technology Austria, 2020. date_created: 2020-05-29T08:27:32Z date_published: 2020-06-05T00:00:00Z date_updated: 2023-10-18T08:45:16Z day: '05' ddc: - '570' degree_awarded: PhD department: - _id: SiHi doi: 10.15479/AT:ISTA:7902 ec_funded: 1 file: - access_level: closed checksum: 43c172bf006c95b65992d473c7240d13 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: xcontreras date_created: 2020-06-05T08:18:08Z date_updated: 2021-06-07T22:30:03Z embargo_to: open_access file_id: '7927' file_name: PhDThesis_Contreras.docx file_size: 53134142 relation: source_file - access_level: open_access checksum: addfed9128271be05cae3608e03a6ec0 content_type: application/pdf creator: xcontreras date_created: 2020-06-05T08:18:07Z date_updated: 2021-06-07T22:30:03Z embargo: 2021-06-06 file_id: '7928' file_name: PhDThesis_Contreras.pdf file_size: 35117191 relation: main_file file_date_updated: 2021-06-07T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '214' 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_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6830' relation: dissertation_contains status: public - id: '28' relation: dissertation_contains status: public - id: '7815' relation: dissertation_contains status: public status: public supervisor: - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 title: Genetic dissection of neural development in health and disease at single cell resolution type: dissertation user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ...