[{"file_date_updated":"2020-09-24T07:03:20Z","article_processing_charge":"No","oa_version":"Published Version","oa":1,"language":[{"iso":"eng"}],"pmid":1,"year":"2020","date_published":"2020-03-11T00:00:00Z","citation":{"ieee":"H. M. Moon, S. Hippenmeyer, L. Luo, and A. Wynshaw-Boris, “LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","chicago":"Moon, Hyang Mi, Simon Hippenmeyer, Liqun Luo, and Anthony Wynshaw-Boris. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.51512\">https://doi.org/10.7554/elife.51512</a>.","short":"H.M. Moon, S. Hippenmeyer, L. Luo, A. Wynshaw-Boris, ELife 9 (2020).","ama":"Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.51512\">10.7554/elife.51512</a>","apa":"Moon, H. M., Hippenmeyer, S., Luo, L., &#38; Wynshaw-Boris, A. (2020). LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.51512\">https://doi.org/10.7554/elife.51512</a>","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.” <i>ELife</i>, vol. 9, 51512, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.51512\">10.7554/elife.51512</a>."},"_id":"7593","status":"public","quality_controlled":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication":"eLife","article_type":"original","day":"11","has_accepted_license":"1","article_number":"51512","external_id":{"pmid":["32159512"],"isi":["000522835800001"]},"publication_status":"published","isi":1,"doi":"10.7554/elife.51512","main_file_link":[{"url":"https://doi.org/10.1101/751958","open_access":"1"}],"publisher":"eLife Sciences Publications","department":[{"_id":"SiHi"}],"intvolume":"         9","date_updated":"2023-08-18T07:06:31Z","author":[{"last_name":"Moon","full_name":"Moon, Hyang Mi","first_name":"Hyang Mi"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"full_name":"Luo, Liqun","first_name":"Liqun","last_name":"Luo"},{"first_name":"Anthony","full_name":"Wynshaw-Boris, Anthony","last_name":"Wynshaw-Boris"}],"date_created":"2020-03-20T13:16:41Z","file":[{"success":1,"date_created":"2020-09-24T07:03:20Z","content_type":"application/pdf","date_updated":"2020-09-24T07:03:20Z","access_level":"open_access","relation":"main_file","file_name":"2020_elife_Moon.pdf","creator":"dernst","checksum":"396ceb2dd10b102ef4e699666b9342c3","file_id":"8567","file_size":15089438}],"fulldoi":"https://doi.org/10.7554/elife.51512","type":"journal_article","abstract":[{"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.","lang":"eng"}],"volume":9,"title":"LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility","month":"03","publication_identifier":{"issn":["2050-084X"]},"license":"https://creativecommons.org/licenses/by/4.0/","ddc":["570"]},{"language":[{"iso":"eng"}],"year":"2020","date_published":"2020-05-08T00:00:00Z","oa":1,"article_processing_charge":"No","oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"file_date_updated":"2020-07-14T12:48:03Z","has_accepted_license":"1","article_number":"48","ec_funded":1,"publication":"Frontiers in Education","article_type":"original","day":"08","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","citation":{"short":"R.J. Beattie, S. Hippenmeyer, F. Pauler, Frontiers in Education 5 (2020).","ieee":"R. J. Beattie, S. Hippenmeyer, and F. Pauler, “SCOPES: Sparking curiosity through Open-Source platforms in education and science,” <i>Frontiers in Education</i>, vol. 5. Frontiers Media, 2020.","chicago":"Beattie, Robert J, Simon Hippenmeyer, and Florian Pauler. “SCOPES: Sparking Curiosity through Open-Source Platforms in Education and Science.” <i>Frontiers in Education</i>. Frontiers Media, 2020. <a href=\"https://doi.org/10.3389/feduc.2020.00048\">https://doi.org/10.3389/feduc.2020.00048</a>.","mla":"Beattie, Robert J., et al. “SCOPES: Sparking Curiosity through Open-Source Platforms in Education and Science.” <i>Frontiers in Education</i>, vol. 5, 48, Frontiers Media, 2020, doi:<a href=\"https://doi.org/10.3389/feduc.2020.00048\">10.3389/feduc.2020.00048</a>.","apa":"Beattie, R. J., Hippenmeyer, S., &#38; Pauler, F. (2020). SCOPES: Sparking curiosity through Open-Source platforms in education and science. <i>Frontiers in Education</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/feduc.2020.00048\">https://doi.org/10.3389/feduc.2020.00048</a>","ista":"Beattie RJ, Hippenmeyer S, Pauler F. 2020. SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. 5, 48.","ama":"Beattie RJ, Hippenmeyer S, Pauler F. SCOPES: Sparking curiosity through Open-Source platforms in education and science. <i>Frontiers in Education</i>. 2020;5. doi:<a href=\"https://doi.org/10.3389/feduc.2020.00048\">10.3389/feduc.2020.00048</a>"},"_id":"7814","status":"public","quality_controlled":"1","publisher":"Frontiers Media","department":[{"_id":"SiHi"}],"intvolume":"         5","date_updated":"2024-10-22T10:46:38Z","author":[{"last_name":"Beattie","orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J","first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"},{"last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian"}],"date_created":"2020-05-11T08:18:48Z","doi":"10.3389/feduc.2020.00048","publication_status":"published","corr_author":"1","ddc":["570"],"title":"SCOPES: Sparking curiosity through Open-Source platforms in education and science","month":"05","publication_identifier":{"issn":["2504-284X"]},"type":"journal_article","fulldoi":"https://doi.org/10.3389/feduc.2020.00048","abstract":[{"lang":"eng","text":"Scientific research is to date largely restricted to wealthy laboratories in developed nations due to the necessity of complex and expensive equipment. This inequality limits the capacity of science to be used as a diplomatic channel. Maker movements use open-source technologies including additive manufacturing (3D printing) and laser cutting, together with low-cost computers for developing novel products. This movement is setting the groundwork for a revolution, allowing scientific equipment to be sourced at a fraction of the cost and has the potential to increase the availability of equipment for scientists around the world. Science education is increasingly recognized as another channel for science diplomacy. In this perspective, we introduce the idea that the Maker movement and open-source technologies have the potential to revolutionize science, technology, engineering and mathematics (STEM) education worldwide. We present an open-source STEM didactic tool called SCOPES (Sparking Curiosity through Open-source Platforms in Education and Science). SCOPES is self-contained, independent of local resources, and cost-effective. SCOPES can be adapted to communicate complex subjects from genetics to neurobiology, perform real-world biological experiments and explore digitized scientific samples. We envision such platforms will enhance science diplomacy by providing a means for scientists to share their findings with classrooms and for educators to incorporate didactic concepts into STEM lessons. By providing students the opportunity to design, perform, and share scientific experiments, students also experience firsthand the benefits of a multinational scientific community. We provide instructions on how to build and use SCOPES on our webpage: http://scopeseducation.org."}],"volume":5,"file":[{"file_name":"2020_FrontiersEduc_Beattie.pdf","relation":"main_file","access_level":"open_access","content_type":"application/pdf","date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-11T11:34:08Z","file_id":"7818","file_size":1402146,"checksum":"a24ec24e38d843341ae620ec76c53688","creator":"dernst"}],"project":[{"grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex","_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}]},{"file_date_updated":"2021-12-02T12:35:12Z","oa_version":"Published Version","article_processing_charge":"No","oa":1,"year":"2020","date_published":"2020-09-15T00:00:00Z","pmid":1,"language":[{"iso":"eng"}],"_id":"8093","citation":{"ama":"Hippe A, Braun SA, Oláh P, et al. EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. <i>British Journal of Cancer</i>. 2020;123:942-954. doi:<a href=\"https://doi.org/10.1038/s41416-020-0943-2\">10.1038/s41416-020-0943-2</a>","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.","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. <i>British Journal of Cancer</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41416-020-0943-2\">https://doi.org/10.1038/s41416-020-0943-2</a>","mla":"Hippe, Andreas, et al. “EGFR/Ras-Induced CCL20 Production Modulates the Tumour Microenvironment.” <i>British Journal of Cancer</i>, vol. 123, Springer Nature, 2020, pp. 942–54, doi:<a href=\"https://doi.org/10.1038/s41416-020-0943-2\">10.1038/s41416-020-0943-2</a>.","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.” <i>British Journal of Cancer</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41416-020-0943-2\">https://doi.org/10.1038/s41416-020-0943-2</a>.","ieee":"A. Hippe <i>et al.</i>, “EGFR/Ras-induced CCL20 production modulates the tumour microenvironment,” <i>British Journal of Cancer</i>, vol. 123. Springer Nature, pp. 942–954, 2020.","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."},"quality_controlled":"1","status":"public","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","publication":"British Journal of Cancer","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"15","article_type":"original","has_accepted_license":"1","external_id":{"pmid":["32601464"],"isi":["000544152500001"]},"publication_status":"published","isi":1,"doi":"10.1038/s41416-020-0943-2","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.","page":"942-954","publisher":"Springer Nature","date_created":"2020-07-05T22:00:46Z","author":[{"first_name":"Andreas","full_name":"Hippe, Andreas","last_name":"Hippe"},{"full_name":"Braun, Stephan Alexander","first_name":"Stephan Alexander","last_name":"Braun"},{"last_name":"Oláh","full_name":"Oláh, Péter","first_name":"Péter"},{"full_name":"Gerber, Peter Arne","first_name":"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"},{"last_name":"Holtz","first_name":"Stephanie","full_name":"Holtz, Stephanie"},{"first_name":"Katharina","full_name":"Jannasch, Katharina","last_name":"Jannasch"},{"last_name":"Pivarcsi","full_name":"Pivarcsi, Andor","first_name":"Andor"},{"last_name":"Buhren","full_name":"Buhren, Bettina","first_name":"Bettina"},{"last_name":"Schrumpf","first_name":"Holger","full_name":"Schrumpf, Holger"},{"first_name":"Andreas","full_name":"Kislat, Andreas","last_name":"Kislat"},{"last_name":"Bünemann","full_name":"Bünemann, Erich","first_name":"Erich"},{"full_name":"Steinhoff, Martin","first_name":"Martin","last_name":"Steinhoff"},{"last_name":"Fischer","first_name":"Jens","full_name":"Fischer, Jens"},{"last_name":"Lira","first_name":"Sérgio A.","full_name":"Lira, Sérgio A."},{"first_name":"Petra","full_name":"Boukamp, Petra","last_name":"Boukamp"},{"full_name":"Hevezi, Peter","first_name":"Peter","last_name":"Hevezi"},{"first_name":"Nikolas Hendrik","full_name":"Stoecklein, Nikolas Hendrik","last_name":"Stoecklein"},{"last_name":"Hoffmann","full_name":"Hoffmann, Thomas","first_name":"Thomas"},{"last_name":"Alves","full_name":"Alves, Frauke","first_name":"Frauke"},{"last_name":"Sleeman","full_name":"Sleeman, Jonathan","first_name":"Jonathan"},{"first_name":"Thomas","full_name":"Bauer, Thomas","last_name":"Bauer"},{"first_name":"Jörg","full_name":"Klufa, Jörg","last_name":"Klufa"},{"last_name":"Amberg","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole"},{"last_name":"Sibilia","full_name":"Sibilia, Maria","first_name":"Maria"},{"last_name":"Zlotnik","full_name":"Zlotnik, Albert","first_name":"Albert"},{"full_name":"Müller-Homey, Anja","first_name":"Anja","last_name":"Müller-Homey"},{"first_name":"Bernhard","full_name":"Homey, Bernhard","last_name":"Homey"}],"intvolume":"       123","date_updated":"2023-08-22T07:51:12Z","department":[{"_id":"SiHi"}],"file":[{"access_level":"open_access","date_created":"2021-12-02T12:35:12Z","success":1,"date_updated":"2021-12-02T12:35:12Z","content_type":"application/pdf","file_name":"2020_BrJournalCancer_Hippe.pdf","relation":"main_file","creator":"cchlebak","file_size":3620691,"file_id":"10398","checksum":"05a8e65d49c3f5b8e37ac4afe68287e2"}],"abstract":[{"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.","lang":"eng"}],"volume":123,"type":"journal_article","fulldoi":"https://doi.org/10.1038/s41416-020-0943-2","month":"09","title":"EGFR/Ras-induced CCL20 production modulates the tumour microenvironment","publication_identifier":{"issn":["0007-0920"],"eissn":["1532-1827"]},"related_material":{"record":[{"relation":"later_version","id":"10170","status":"deleted"}],"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41416-021-01563-y"}]},"ddc":["610"]},{"has_accepted_license":"1","ec_funded":1,"article_type":"original","publication":"Neuron","day":"23","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"status":"public","quality_controlled":"1","citation":{"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.","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.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>.","ieee":"S. Laukoter <i>et al.</i>, “Cell-type specificity of genomic imprinting in cerebral cortex,” <i>Neuron</i>, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.","mla":"Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>.","ama":"Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. 2020;107(6):1160-1179.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>","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. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>","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."},"_id":"8162","pmid":1,"language":[{"iso":"eng"}],"year":"2020","date_published":"2020-09-23T00:00:00Z","oa":1,"article_processing_charge":"No","oa_version":"Published Version","file_date_updated":"2020-12-02T09:26:46Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"ddc":["570"],"related_material":{"link":[{"relation":"press_release","description":"News on IST Website","url":"https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/"}]},"publication_identifier":{"issn":["0896-6273"]},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","title":"Cell-type specificity of genomic imprinting in cerebral cortex","month":"09","type":"journal_article","fulldoi":"https://doi.org/10.1016/j.neuron.2020.06.031","volume":107,"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."}],"project":[{"grant_number":"24812","name":"Molecular mechanisms of radial neuronal migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"},{"grant_number":"T01031","name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex","grant_number":"M02416"},{"grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","_id":"25D92700-B435-11E9-9278-68D0E5697425"},{"_id":"25D7962E-B435-11E9-9278-68D0E5697425","name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014"},{"grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"file":[{"file_id":"8828","file_size":8911830,"checksum":"7becdc16a6317304304631087ae7dd7f","creator":"dernst","file_name":"2020_Neuron_Laukoter.pdf","relation":"main_file","access_level":"open_access","date_updated":"2020-12-02T09:26:46Z","content_type":"application/pdf","date_created":"2020-12-02T09:26:46Z","success":1}],"intvolume":"       107","date_updated":"2025-06-12T07:19:46Z","department":[{"_id":"SiHi"}],"date_created":"2020-07-23T16:03:12Z","author":[{"full_name":"Laukoter, Susanne","orcid":"0000-0002-7903-3010","first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler"},{"last_name":"Beattie","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Amberg","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207"},{"full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"first_name":"Thomas","full_name":"Penz, Thomas","last_name":"Penz"},{"full_name":"Bock, Christoph","orcid":"0000-0001-6091-3088","first_name":"Christoph","last_name":"Bock"},{"last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"publisher":"Elsevier","page":"1160-1179.e9","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.","doi":"10.1016/j.neuron.2020.06.031","isi":1,"publication_status":"published","issue":"6","corr_author":"1","external_id":{"isi":["000579698700006"],"pmid":["32707083"]}},{"isi":1,"publication_status":"published","external_id":{"isi":["000573860700001"],"pmid":["33173731"]},"issue":"21","author":[{"last_name":"Tian","full_name":"Tian, Anhao","first_name":"Anhao"},{"full_name":"Kang, Bo","first_name":"Bo","last_name":"Kang"},{"first_name":"Baizhou","full_name":"Li, Baizhou","last_name":"Li"},{"last_name":"Qiu","full_name":"Qiu, Biying","first_name":"Biying"},{"full_name":"Jiang, Wenhong","first_name":"Wenhong","last_name":"Jiang"},{"last_name":"Shao","full_name":"Shao, Fangjie","first_name":"Fangjie"},{"last_name":"Gao","full_name":"Gao, Qingqing","first_name":"Qingqing"},{"first_name":"Rui","full_name":"Liu, Rui","last_name":"Liu"},{"last_name":"Cai","first_name":"Chengwei","full_name":"Cai, Chengwei"},{"last_name":"Jing","full_name":"Jing, Rui","first_name":"Rui"},{"first_name":"Wei","full_name":"Wang, Wei","last_name":"Wang"},{"last_name":"Chen","full_name":"Chen, Pengxiang","first_name":"Pengxiang"},{"full_name":"Liang, Qinghui","first_name":"Qinghui","last_name":"Liang"},{"last_name":"Bao","full_name":"Bao, Lili","first_name":"Lili"},{"last_name":"Man","full_name":"Man, Jianghong","first_name":"Jianghong"},{"last_name":"Wang","first_name":"Yan","full_name":"Wang, Yan"},{"first_name":"Yu","full_name":"Shi, Yu","last_name":"Shi"},{"full_name":"Li, Jin","first_name":"Jin","last_name":"Li"},{"last_name":"Yang","full_name":"Yang, Minmin","first_name":"Minmin"},{"last_name":"Wang","full_name":"Wang, Lisha","first_name":"Lisha"},{"first_name":"Jianmin","full_name":"Zhang, Jianmin","last_name":"Zhang"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"last_name":"Zhu","first_name":"Junming","full_name":"Zhu, Junming"},{"full_name":"Bian, Xiuwu","first_name":"Xiuwu","last_name":"Bian"},{"full_name":"Wang, Ying‐Jie","first_name":"Ying‐Jie","last_name":"Wang"},{"full_name":"Liu, Chong","first_name":"Chong","last_name":"Liu"}],"date_created":"2020-10-01T09:44:13Z","department":[{"_id":"SiHi"}],"date_updated":"2025-06-12T06:59:38Z","intvolume":"         7","publisher":"Wiley","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.","doi":"10.1002/advs.202001724","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."}],"volume":7,"type":"journal_article","fulldoi":"https://doi.org/10.1002/advs.202001724","project":[{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"file":[{"checksum":"92818c23ecc70e35acfa671f3cfb9909","file_size":7835833,"file_id":"8938","creator":"dernst","relation":"main_file","file_name":"2020_AdvScience_Tian.pdf","success":1,"date_created":"2020-12-10T14:07:24Z","date_updated":"2020-12-10T14:07:24Z","content_type":"application/pdf","access_level":"open_access"}],"ddc":["570"],"publication_identifier":{"issn":["2198-3844"]},"month":"11","title":"Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting","keyword":["General Engineering","General Physics and Astronomy","General Materials Science","Medicine (miscellaneous)","General Chemical Engineering","Biochemistry","Genetics and Molecular Biology (miscellaneous)"],"oa_version":"Published Version","article_processing_charge":"No","file_date_updated":"2020-12-10T14:07:24Z","date_published":"2020-11-04T00:00:00Z","year":"2020","pmid":1,"language":[{"iso":"eng"}],"oa":1,"scopus_import":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"quality_controlled":"1","status":"public","_id":"8592","citation":{"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. <i>Advanced Science</i>. Wiley. <a href=\"https://doi.org/10.1002/advs.202001724\">https://doi.org/10.1002/advs.202001724</a>","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.","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. <i>Advanced Science</i>. 2020;7(21). doi:<a href=\"https://doi.org/10.1002/advs.202001724\">10.1002/advs.202001724</a>","mla":"Tian, Anhao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.” <i>Advanced Science</i>, vol. 7, no. 21, 2001724, Wiley, 2020, doi:<a href=\"https://doi.org/10.1002/advs.202001724\">10.1002/advs.202001724</a>.","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.” <i>Advanced Science</i>. Wiley, 2020. <a href=\"https://doi.org/10.1002/advs.202001724\">https://doi.org/10.1002/advs.202001724</a>.","ieee":"A. Tian <i>et al.</i>, “Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting,” <i>Advanced Science</i>, vol. 7, no. 21. Wiley, 2020.","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)."},"ec_funded":1,"has_accepted_license":"1","article_number":"2001724","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"04","article_type":"original","publication":"Advanced Science"},{"year":"2020","date_published":"2020-12-11T00:00:00Z","language":[{"iso":"eng"}],"pmid":1,"oa":1,"oa_version":"Published Version","article_processing_charge":"No","file_date_updated":"2020-12-14T08:09:43Z","ec_funded":1,"has_accepted_license":"1","article_number":"2662","article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Cells","day":"11","scopus_import":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"quality_controlled":"1","status":"public","_id":"8949","citation":{"short":"X. Zhang, C.V. Mennicke, G. Xiao, R.J. Beattie, M. Haider, S. Hippenmeyer, H.T. Ghashghaei, Cells 9 (2020).","ieee":"X. Zhang <i>et al.</i>, “Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage,” <i>Cells</i>, vol. 9, no. 12. MDPI, 2020.","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.” <i>Cells</i>. MDPI, 2020. <a href=\"https://doi.org/10.3390/cells9122662\">https://doi.org/10.3390/cells9122662</a>.","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.” <i>Cells</i>, vol. 9, no. 12, 2662, MDPI, 2020, doi:<a href=\"https://doi.org/10.3390/cells9122662\">10.3390/cells9122662</a>.","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. <i>Cells</i>. 2020;9(12). doi:<a href=\"https://doi.org/10.3390/cells9122662\">10.3390/cells9122662</a>","apa":"Zhang, X., Mennicke, C. V., Xiao, G., Beattie, R. J., Haider, M., Hippenmeyer, S., &#38; Ghashghaei, H. T. (2020). Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. <i>Cells</i>. MDPI. <a href=\"https://doi.org/10.3390/cells9122662\">https://doi.org/10.3390/cells9122662</a>","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."},"date_created":"2020-12-14T08:04:03Z","author":[{"full_name":"Zhang, Xuying","first_name":"Xuying","last_name":"Zhang"},{"last_name":"Mennicke","first_name":"Christine V.","full_name":"Mennicke, Christine V."},{"full_name":"Xiao, Guanxi","first_name":"Guanxi","last_name":"Xiao"},{"first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J","last_name":"Beattie"},{"full_name":"Haider, Mansoor","first_name":"Mansoor","last_name":"Haider"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"last_name":"Ghashghaei","full_name":"Ghashghaei, H. Troy","first_name":"H. Troy"}],"department":[{"_id":"SiHi"}],"intvolume":"         9","date_updated":"2025-06-12T07:02:43Z","publisher":"MDPI","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.","doi":"10.3390/cells9122662","isi":1,"publication_status":"published","external_id":{"isi":["000601787300001"],"pmid":["33322301"]},"issue":"12","ddc":["570"],"publication_identifier":{"issn":["2073-4409"]},"month":"12","title":"Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage","abstract":[{"text":"<jats:p>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.</jats:p>","lang":"eng"}],"volume":9,"type":"journal_article","fulldoi":"https://doi.org/10.3390/cells9122662","project":[{"name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex","grant_number":"M02416","_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"file":[{"creator":"dernst","checksum":"5095cbdc728c9a510c5761cf60a8861c","file_size":3504525,"file_id":"8950","content_type":"application/pdf","date_updated":"2020-12-14T08:09:43Z","success":1,"date_created":"2020-12-14T08:09:43Z","access_level":"open_access","relation":"main_file","file_name":"2020_Cells_Zhang.pdf"}]},{"date_updated":"2025-04-15T08:23:06Z","intvolume":"         1","department":[{"_id":"SiHi"}],"date_created":"2020-12-30T10:17:07Z","author":[{"orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter"},{"first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg"},{"full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","last_name":"Pauler"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"}],"publisher":"Elsevier","acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical Facilities (PCF). N.A received support from the FWF Firnberg-Programm (T 1031). This work was also supported by IST Austria institutional funds; FWF SFB F78 to S.H.; NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 618444 to S.H.; 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.","doi":"10.1016/j.xpro.2020.100215","publication_status":"published","issue":"3","corr_author":"1","external_id":{"pmid":["33377108"]},"ddc":["570"],"publication_identifier":{"issn":["2666-1667"]},"title":"Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy","month":"12","fulldoi":"https://doi.org/10.1016/j.xpro.2020.100215","type":"journal_article","volume":1,"abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) technology enables concomitant fluorescent cell labeling and induction of uniparental chromosome disomy (UPD) with single-cell resolution. In UPD, imprinted genes are either overexpressed 2-fold or are not expressed. Here, the MADM platform is utilized to probe imprinting phenotypes at the transcriptional level. This protocol highlights major steps for the generation and isolation of projection neurons and astrocytes with MADM-induced UPD from mouse cerebral cortex for downstream single-cell and low-input sample RNA-sequencing experiments.\r\n\r\nFor complete details on the use and execution of this protocol, please refer to Laukoter et al. (2020b)."}],"project":[{"name":"Role of Eed in neural stem cell lineage progression","grant_number":"T01031","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"},{"grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"file":[{"relation":"main_file","file_name":"2020_STARProtocols_Laukoter.pdf","date_updated":"2021-01-07T15:57:27Z","content_type":"application/pdf","success":1,"date_created":"2021-01-07T15:57:27Z","access_level":"open_access","checksum":"f1e9a433e9cb0f41f7b6df6b76db1f6e","file_id":"8996","file_size":4031449,"creator":"dernst"}],"language":[{"iso":"eng"}],"pmid":1,"year":"2020","date_published":"2020-12-18T00:00:00Z","oa":1,"article_processing_charge":"No","oa_version":"Published Version","file_date_updated":"2021-01-07T15:57:27Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"article_number":"100215","has_accepted_license":"1","ec_funded":1,"publication":"STAR Protocols","article_type":"original","day":"18","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"status":"public","quality_controlled":"1","citation":{"short":"S. Laukoter, N. Amberg, F. Pauler, S. Hippenmeyer, STAR Protocols 1 (2020).","chicago":"Laukoter, Susanne, Nicole Amberg, Florian Pauler, and Simon Hippenmeyer. “Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome Disomy.” <i>STAR Protocols</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">https://doi.org/10.1016/j.xpro.2020.100215</a>.","ieee":"S. Laukoter, N. Amberg, F. Pauler, and S. Hippenmeyer, “Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy,” <i>STAR Protocols</i>, vol. 1, no. 3. Elsevier, 2020.","mla":"Laukoter, Susanne, et al. “Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome Disomy.” <i>STAR Protocols</i>, vol. 1, no. 3, 100215, Elsevier, 2020, doi:<a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">10.1016/j.xpro.2020.100215</a>.","apa":"Laukoter, S., Amberg, N., Pauler, F., &#38; Hippenmeyer, S. (2020). Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">https://doi.org/10.1016/j.xpro.2020.100215</a>","ista":"Laukoter S, Amberg N, Pauler F, Hippenmeyer S. 2020. Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. STAR Protocols. 1(3), 100215.","ama":"Laukoter S, Amberg N, Pauler F, Hippenmeyer S. Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. <i>STAR Protocols</i>. 2020;1(3). doi:<a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">10.1016/j.xpro.2020.100215</a>"},"_id":"8978"},{"publisher":"Springer Nature","date_updated":"2025-06-12T07:30:49Z","department":[{"_id":"SiHi"}],"intvolume":"        11","author":[{"id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","last_name":"Laukoter"},{"last_name":"Beattie","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753"},{"last_name":"Pauler","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg"},{"full_name":"Nakayama, Keiichi I.","first_name":"Keiichi I.","last_name":"Nakayama"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer"}],"date_created":"2020-01-11T10:42:48Z","doi":"10.1038/s41467-019-14077-2","publication_status":"published","isi":1,"corr_author":"1","external_id":{"pmid":["31924768"],"isi":["000551459000005"]},"ddc":["570"],"title":"Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development","month":"01","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/"}]},"publication_identifier":{"issn":["2041-1723"]},"fulldoi":"https://doi.org/10.1038/s41467-019-14077-2","type":"journal_article","volume":11,"abstract":[{"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.","lang":"eng"}],"project":[{"grant_number":"T01031","name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"},{"grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"},{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425"}],"file":[{"file_name":"2020_NatureComm_Laukoter.pdf","relation":"main_file","access_level":"open_access","date_updated":"2020-07-14T12:47:54Z","content_type":"application/pdf","date_created":"2020-01-13T07:42:31Z","file_size":8063333,"file_id":"7261","checksum":"ebf1ed522f4e0be8d94c939c1806a709","creator":"dernst"}],"pmid":1,"language":[{"iso":"eng"}],"date_published":"2020-01-10T00:00:00Z","year":"2020","oa":1,"article_processing_charge":"No","oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"}],"file_date_updated":"2020-07-14T12:47:54Z","has_accepted_license":"1","article_number":"195","ec_funded":1,"publication":"Nature Communications","article_type":"original","day":"10","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","citation":{"mla":"Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” <i>Nature Communications</i>, vol. 11, 195, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1038/s41467-019-14077-2\">10.1038/s41467-019-14077-2</a>.","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. <i>Nature Communications</i>. 2020;11. doi:<a href=\"https://doi.org/10.1038/s41467-019-14077-2\">10.1038/s41467-019-14077-2</a>","apa":"Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., &#38; Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-019-14077-2\">https://doi.org/10.1038/s41467-019-14077-2</a>","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.","short":"S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer, Nature Communications 11 (2020).","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,” <i>Nature Communications</i>, vol. 11. Springer Nature, 2020.","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.” <i>Nature Communications</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41467-019-14077-2\">https://doi.org/10.1038/s41467-019-14077-2</a>."},"_id":"7253","status":"public","quality_controlled":"1"},{"month":"11","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"bioRxiv","day":"05","title":"Novel imprints in mouse blastocysts are predominantly DNA methylation independent","abstract":[{"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.","lang":"eng"}],"fulldoi":"https://doi.org/10.1101/2020.11.03.366948","type":"preprint","status":"public","_id":"8813","citation":{"ama":"Santini L, Halbritter F, Titz-Teixeira F, et al. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.11.03.366948\">10.1101/2020.11.03.366948</a>","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, <a href=\"https://doi.org/10.1101/2020.11.03.366948\">10.1101/2020.11.03.366948</a>.","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. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2020.11.03.366948\">https://doi.org/10.1101/2020.11.03.366948</a>","mla":"Santini, Laura, et al. “Novel Imprints in Mouse Blastocysts Are Predominantly DNA Methylation Independent.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2020.11.03.366948\">10.1101/2020.11.03.366948</a>.","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.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2020.11.03.366948\">https://doi.org/10.1101/2020.11.03.366948</a>.","ieee":"L. Santini <i>et al.</i>, “Novel imprints in mouse blastocysts are predominantly DNA methylation independent,” <i>bioRxiv</i>. .","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.)."},"year":"2020","date_published":"2020-11-05T00:00:00Z","date_created":"2020-11-26T07:17:19Z","author":[{"full_name":"Santini, Laura","first_name":"Laura","last_name":"Santini"},{"last_name":"Halbritter","first_name":"Florian","full_name":"Halbritter, Florian"},{"last_name":"Titz-Teixeira","full_name":"Titz-Teixeira, Fabian","first_name":"Fabian"},{"full_name":"Suzuki, Toru","first_name":"Toru","last_name":"Suzuki"},{"last_name":"Asami","full_name":"Asami, Maki","first_name":"Maki"},{"last_name":"Ramesmayer","full_name":"Ramesmayer, Julia","first_name":"Julia"},{"first_name":"Xiaoyan","full_name":"Ma, Xiaoyan","last_name":"Ma"},{"full_name":"Lackner, Andreas","first_name":"Andreas","last_name":"Lackner"},{"first_name":"Nick","full_name":"Warr, Nick","last_name":"Warr"},{"orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"last_name":"Laue","full_name":"Laue, Ernest","first_name":"Ernest"},{"full_name":"Farlik, Matthias","first_name":"Matthias","last_name":"Farlik"},{"full_name":"Bock, Christoph","first_name":"Christoph","last_name":"Bock"},{"full_name":"Beyer, Andreas","first_name":"Andreas","last_name":"Beyer"},{"first_name":"Anthony C. F.","full_name":"Perry, Anthony C. F.","last_name":"Perry"},{"last_name":"Leeb","first_name":"Martin","full_name":"Leeb, Martin"}],"date_updated":"2026-07-06T12:45:07Z","language":[{"iso":"eng"}],"pmid":1,"department":[{"_id":"SiHi"}],"main_file_link":[{"url":"https://doi.org/10.1101/2020.11.03.366948","open_access":"1"}],"oa":1,"doi":"10.1101/2020.11.03.366948","das_tickbox":"1","oa_version":"Preprint","article_processing_charge":"No","publication_status":"submitted","external_id":{"pmid":["PPR234457 "]}},{"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","_id":"7815","citation":{"short":"R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen, S. Hippenmeyer, Journal of Visual Experiments (2020).","ieee":"R. J. Beattie <i>et al.</i>, “Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM),” <i>Journal of Visual Experiments</i>, no. 159. MyJove Corporation, 2020.","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).” <i>Journal of Visual Experiments</i>. MyJove Corporation, 2020. <a href=\"https://doi.org/10.3791/61147\">https://doi.org/10.3791/61147</a>.","mla":"Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” <i>Journal of Visual Experiments</i>, no. 159, e61147, MyJove Corporation, 2020, doi:<a href=\"https://doi.org/10.3791/61147\">10.3791/61147</a>.","apa":"Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen, A. H., &#38; Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). <i>Journal of Visual Experiments</i>. MyJove Corporation. <a href=\"https://doi.org/10.3791/61147\">https://doi.org/10.3791/61147</a>","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.","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). <i>Journal of Visual Experiments</i>. 2020;(159). doi:<a href=\"https://doi.org/10.3791/61147\">10.3791/61147</a>"},"quality_controlled":"1","status":"public","ec_funded":1,"article_number":"e61147","has_accepted_license":"1","day":"08","article_type":"original","publication":"Journal of Visual Experiments","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","article_processing_charge":"No","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"file_date_updated":"2020-07-14T12:48:03Z","date_published":"2020-05-08T00:00:00Z","year":"2020","language":[{"iso":"eng"}],"pmid":1,"oa":1,"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."}],"fulldoi":"https://doi.org/10.3791/61147","type":"journal_article","project":[{"_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"},{"call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T01031","name":"Role of Eed in neural stem cell lineage progression"},{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of radial neuronal migration","grant_number":"24812"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"file":[{"access_level":"open_access","date_created":"2020-05-11T08:28:38Z","content_type":"application/pdf","date_updated":"2020-07-14T12:48:03Z","file_name":"jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf","relation":"main_file","creator":"rbeattie","file_id":"7816","file_size":1352186,"checksum":"3154ea7f90b9fb45e084cd1c2770597d"}],"ddc":["570"],"month":"05","title":"Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM)","publication_identifier":{"issn":["1940-087X"]},"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"7902"}]},"publication_status":"published","isi":1,"corr_author":"1","external_id":{"isi":["000546406600043"],"pmid":["32449730"]},"issue":"159","publisher":"MyJove Corporation","author":[{"full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","last_name":"Beattie"},{"last_name":"Streicher","full_name":"Streicher, Carmen","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"last_name":"Cheung","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T"},{"last_name":"Contreras","full_name":"Contreras, Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","first_name":"Ximena"},{"first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H","last_name":"Hansen"},{"last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"}],"date_created":"2020-05-11T08:31:20Z","date_updated":"2026-11-11T23:30:19Z","department":[{"_id":"SiHi"}],"doi":"10.3791/61147"},{"date_published":"2020-06-05T00:00:00Z","year":"2020","language":[{"iso":"eng"}],"degree_awarded":"PhD","oa":1,"oa_version":"Published Version","article_processing_charge":"No","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"file_date_updated":"2021-06-07T22:30:03Z","ec_funded":1,"has_accepted_license":"1","day":"05","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","alternative_title":["ISTA Thesis"],"_id":"7902","citation":{"mla":"Contreras, Ximena. <i>Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7902\">10.15479/AT:ISTA:7902</a>.","apa":"Contreras, X. (2020). <i>Genetic dissection of neural development in health and disease at single cell resolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7902\">https://doi.org/10.15479/AT:ISTA:7902</a>","ista":"Contreras X. 2020. Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria.","ama":"Contreras X. Genetic dissection of neural development in health and disease at single cell resolution. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7902\">10.15479/AT:ISTA:7902</a>","short":"X. Contreras, Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution, Institute of Science and Technology Austria, 2020.","ieee":"X. Contreras, “Genetic dissection of neural development in health and disease at single cell resolution,” Institute of Science and Technology Austria, 2020.","chicago":"Contreras, Ximena. “Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7902\">https://doi.org/10.15479/AT:ISTA:7902</a>."},"status":"public","page":"214","publisher":"Institute of Science and Technology Austria","author":[{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","first_name":"Ximena","full_name":"Contreras, Ximena","last_name":"Contreras"}],"date_created":"2020-05-29T08:27:32Z","department":[{"_id":"SiHi"}],"date_updated":"2026-06-18T19:12:39Z","doi":"10.15479/AT:ISTA:7902","publication_status":"published","OA_place":"publisher","supervisor":[{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer"}],"corr_author":"1","ddc":["570"],"month":"06","title":"Genetic dissection of neural development in health and disease at single cell resolution","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"id":"28","status":"public","relation":"dissertation_contains"},{"status":"public","id":"7815","relation":"dissertation_contains"},{"id":"6830","status":"public","relation":"dissertation_contains"}]},"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."}],"fulldoi":"https://doi.org/10.15479/AT:ISTA:7902","type":"dissertation","file":[{"file_size":53134142,"file_id":"7927","checksum":"43c172bf006c95b65992d473c7240d13","creator":"xcontreras","file_name":"PhDThesis_Contreras.docx","relation":"source_file","access_level":"closed","embargo_to":"open_access","date_created":"2020-06-05T08:18:08Z","date_updated":"2021-06-07T22:30:03Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"},{"checksum":"addfed9128271be05cae3608e03a6ec0","file_size":35117191,"file_id":"7928","creator":"xcontreras","relation":"main_file","file_name":"PhDThesis_Contreras.pdf","date_updated":"2021-06-07T22:30:03Z","content_type":"application/pdf","embargo":"2021-06-06","date_created":"2020-06-05T08:18:07Z","access_level":"open_access"}],"project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}]},{"issue":"9","corr_author":"1","external_id":{"pmid":["33102480"],"isi":["000577915900001"]},"isi":1,"publication_status":"published","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.","doi":"10.3389/fcell.2020.574382","department":[{"_id":"SiHi"}],"date_updated":"2026-11-11T23:30:56Z","intvolume":"         8","author":[{"last_name":"Hansen","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"date_created":"2020-09-26T06:11:07Z","publisher":"Frontiers","project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular mechanisms of radial neuronal migration"},{"grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"}],"file":[{"file_size":5527139,"file_id":"8584","checksum":"01f731824194c94c81a5da360d997073","creator":"dernst","file_name":"2020_Frontiers_Hansen.pdf","relation":"main_file","access_level":"open_access","date_created":"2020-09-28T13:11:17Z","success":1,"date_updated":"2020-09-28T13:11:17Z","content_type":"application/pdf"}],"fulldoi":"https://doi.org/10.3389/fcell.2020.574382","type":"journal_article","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."}],"volume":8,"related_material":{"record":[{"status":"public","id":"9962","relation":"dissertation_contains"}]},"publication_identifier":{"issn":["2296-634X"]},"title":"Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex","month":"09","ddc":["570"],"file_date_updated":"2020-09-28T13:11:17Z","article_processing_charge":"Yes (via OA deal)","oa_version":"Published Version","oa":1,"pmid":1,"language":[{"iso":"eng"}],"date_published":"2020-09-25T00:00:00Z","year":"2020","status":"public","quality_controlled":"1","citation":{"short":"A.H. Hansen, S. Hippenmeyer, Frontiers in Cell and Developmental Biology 8 (2020).","chicago":"Hansen, Andi H, and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” <i>Frontiers in Cell and Developmental Biology</i>. Frontiers, 2020. <a href=\"https://doi.org/10.3389/fcell.2020.574382\">https://doi.org/10.3389/fcell.2020.574382</a>.","ieee":"A. H. Hansen and S. Hippenmeyer, “Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex,” <i>Frontiers in Cell and Developmental Biology</i>, vol. 8, no. 9. Frontiers, 2020.","mla":"Hansen, Andi H., and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” <i>Frontiers in Cell and Developmental Biology</i>, vol. 8, no. 9, 574382, Frontiers, 2020, doi:<a href=\"https://doi.org/10.3389/fcell.2020.574382\">10.3389/fcell.2020.574382</a>.","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.","apa":"Hansen, A. H., &#38; Hippenmeyer, S. (2020). Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. <i>Frontiers in Cell and Developmental Biology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fcell.2020.574382\">https://doi.org/10.3389/fcell.2020.574382</a>","ama":"Hansen AH, Hippenmeyer S. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. <i>Frontiers in Cell and Developmental Biology</i>. 2020;8(9). doi:<a href=\"https://doi.org/10.3389/fcell.2020.574382\">10.3389/fcell.2020.574382</a>"},"_id":"8569","scopus_import":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"day":"25","article_type":"original","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication":"Frontiers in Cell and Developmental Biology","has_accepted_license":"1","article_number":"574382","ec_funded":1},{"abstract":[{"lang":"eng","text":"The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell-type diversity during cortical development. This article is protected by copyright. All rights reserved."}],"volume":149,"fulldoi":"https://doi.org/10.1111/jnc.14601","type":"journal_article","project":[{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425"},{"_id":"25D7962E-B435-11E9-9278-68D0E5697425","grant_number":"RGP0053/2014","name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"file":[{"file_size":889709,"file_id":"7239","checksum":"db027721a95d36f5de36aadcd0bdf7e6","creator":"kschuh","file_name":"2019_Wiley_Amberg.pdf","relation":"main_file","access_level":"open_access","date_created":"2020-01-07T13:35:52Z","content_type":"application/pdf","date_updated":"2020-07-14T12:45:45Z"}],"ddc":["570"],"month":"04","title":"Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex","publication_status":"published","isi":1,"corr_author":"1","external_id":{"isi":["000462680200002"]},"issue":"1","page":"12-26","publisher":"Wiley","date_created":"2018-12-11T11:44:14Z","author":[{"last_name":"Amberg","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"}],"department":[{"_id":"SiHi"}],"intvolume":"       149","date_updated":"2025-04-14T07:43:05Z","doi":"10.1111/jnc.14601","acknowledgement":" This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung \r\nn[f+b]   (C13-002)   to   SH;   a   program   grant   from   the   Human   Frontiers   Science   Program (RGP0053/2014)  to SH;  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, and the  European  Research  Council  (ERC)  under  the  European  Union’s  Horizon  2020  research  and innovation programme (grant agreement No 725780 LinPro)to SH.\r\n","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","_id":"27","citation":{"chicago":"Amberg, Nicole, Susanne Laukoter, and Simon Hippenmeyer. “Epigenetic Cues Modulating the Generation of Cell Type Diversity in the Cerebral Cortex.” <i>Journal of Neurochemistry</i>. Wiley, 2019. <a href=\"https://doi.org/10.1111/jnc.14601\">https://doi.org/10.1111/jnc.14601</a>.","ieee":"N. Amberg, S. Laukoter, and S. Hippenmeyer, “Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex,” <i>Journal of Neurochemistry</i>, vol. 149, no. 1. Wiley, pp. 12–26, 2019.","short":"N. Amberg, S. Laukoter, S. Hippenmeyer, Journal of Neurochemistry 149 (2019) 12–26.","ista":"Amberg N, Laukoter S, Hippenmeyer S. 2019. Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex. Journal of Neurochemistry. 149(1), 12–26.","apa":"Amberg, N., Laukoter, S., &#38; Hippenmeyer, S. (2019). Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex. <i>Journal of Neurochemistry</i>. Wiley. <a href=\"https://doi.org/10.1111/jnc.14601\">https://doi.org/10.1111/jnc.14601</a>","ama":"Amberg N, Laukoter S, Hippenmeyer S. Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex. <i>Journal of Neurochemistry</i>. 2019;149(1):12-26. doi:<a href=\"https://doi.org/10.1111/jnc.14601\">10.1111/jnc.14601</a>","mla":"Amberg, Nicole, et al. “Epigenetic Cues Modulating the Generation of Cell Type Diversity in the Cerebral Cortex.” <i>Journal of Neurochemistry</i>, vol. 149, no. 1, Wiley, 2019, pp. 12–26, doi:<a href=\"https://doi.org/10.1111/jnc.14601\">10.1111/jnc.14601</a>."},"quality_controlled":"1","status":"public","ec_funded":1,"has_accepted_license":"1","publication":"Journal of Neurochemistry","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_type":"review","day":"01","oa_version":"Published Version","article_processing_charge":"Yes (via OA deal)","file_date_updated":"2020-07-14T12:45:45Z","year":"2019","date_published":"2019-04-01T00:00:00Z","language":[{"iso":"eng"}],"oa":1},{"external_id":{"isi":["000459380600001"],"pmid":["30789343"]},"publication_status":"published","isi":1,"doi":"10.7554/eLife.41563","publisher":"eLife Sciences Publications","date_updated":"2023-08-24T14:50:50Z","department":[{"_id":"SiHi"}],"intvolume":"         8","author":[{"last_name":"Henderson","first_name":"Nathan T.","full_name":"Henderson, Nathan T."},{"full_name":"Le Marchand, Sylvain J.","first_name":"Sylvain J.","last_name":"Le Marchand"},{"first_name":"Martin","full_name":"Hruska, Martin","last_name":"Hruska"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"last_name":"Luo","full_name":"Luo, Liqun","first_name":"Liqun"},{"first_name":"Matthew B.","full_name":"Dalva, Matthew B.","last_name":"Dalva"}],"date_created":"2019-03-10T22:59:20Z","file":[{"checksum":"7b0800d003f14cd06b1802dea0c52941","file_id":"6098","file_size":7260753,"creator":"dernst","relation":"main_file","file_name":"2019_eLife_Henderson.pdf","date_updated":"2020-07-14T12:47:19Z","content_type":"application/pdf","date_created":"2019-03-11T16:15:37Z","access_level":"open_access"}],"fulldoi":"https://doi.org/10.7554/eLife.41563","type":"journal_article","abstract":[{"text":"Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control spine density in layer 5 and 6 neurons. MADM cortical neurons in vitro reveal that eB3 controls synapse density independently of action potential-driven activity. Our findings illustrate a new class of competitive mechanism mediated by trans-synaptic organizing proteins which control the number of synapses neurons receive relative to neighboring neurons.","lang":"eng"}],"volume":8,"title":"Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs","month":"02","ddc":["570"],"file_date_updated":"2020-07-14T12:47:19Z","article_processing_charge":"No","oa_version":"Published Version","oa":1,"pmid":1,"language":[{"iso":"eng"}],"date_published":"2019-02-21T00:00:00Z","year":"2019","citation":{"chicago":"Henderson, Nathan T., Sylvain J. Le Marchand, Martin Hruska, Simon Hippenmeyer, Liqun Luo, and Matthew B. Dalva. “Ephrin-B3 Controls Excitatory Synapse Density through Cell-Cell Competition for EphBs.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.41563\">https://doi.org/10.7554/eLife.41563</a>.","ieee":"N. T. Henderson, S. J. Le Marchand, M. Hruska, S. Hippenmeyer, L. Luo, and M. B. Dalva, “Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","short":"N.T. Henderson, S.J. Le Marchand, M. Hruska, S. Hippenmeyer, L. Luo, M.B. Dalva, ELife 8 (2019).","apa":"Henderson, N. T., Le Marchand, S. J., Hruska, M., Hippenmeyer, S., Luo, L., &#38; Dalva, M. B. (2019). Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.41563\">https://doi.org/10.7554/eLife.41563</a>","ista":"Henderson NT, Le Marchand SJ, Hruska M, Hippenmeyer S, Luo L, Dalva MB. 2019. Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs. eLife. 8, e41563.","ama":"Henderson NT, Le Marchand SJ, Hruska M, Hippenmeyer S, Luo L, Dalva MB. Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.41563\">10.7554/eLife.41563</a>","mla":"Henderson, Nathan T., et al. “Ephrin-B3 Controls Excitatory Synapse Density through Cell-Cell Competition for EphBs.” <i>ELife</i>, vol. 8, e41563, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.41563\">10.7554/eLife.41563</a>."},"_id":"6091","status":"public","quality_controlled":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication":"eLife","day":"21","article_number":"e41563","has_accepted_license":"1"},{"fulldoi":"https://doi.org/10.1016/j.isci.2019.04.018","type":"journal_article","abstract":[{"text":"Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis inmice and humans, and its deficiency causes severe skin inflammation, which might affect epidermalstem cell behavior. Here, we describe the inflammation-independent effects of EGFR deficiency dur-ing skin morphogenesis and in adult hair follicle stem cells. Expression and alternative splicing analysisof RNA sequencing data from interfollicular epidermis and outer root sheath indicate that EGFR con-trols genes involved in epidermal differentiation and also in centrosome function, DNA damage, cellcycle, and apoptosis. Genetic experiments employingp53deletion in EGFR-deficient epidermis revealthat EGFR signaling exhibitsp53-dependent functions in proliferative epidermal compartments, aswell asp53-independent functions in differentiated hair shaft keratinocytes. Loss of EGFR leads toabsence of LEF1 protein specifically in the innermost epithelial hair layers, resulting in disorganizationof medulla cells. Thus, our results uncover important spatial and temporal features of cell-autonomousEGFR functions in the epidermis.","lang":"eng"}],"volume":15,"file":[{"date_created":"2019-05-14T11:51:51Z","content_type":"application/pdf","date_updated":"2020-07-14T12:47:30Z","access_level":"open_access","relation":"main_file","file_name":"2019_iScience_Amberg.pdf","creator":"dernst","checksum":"a9ad2296726c9474ad5860c9c2f53622","file_id":"6452","file_size":8365970}],"ddc":["570"],"title":"EGFR controls hair shaft differentiation in a p53-independent manner","month":"05","publication_identifier":{"issn":["2589-0042"]},"publication_status":"published","isi":1,"external_id":{"isi":["000470104600022"]},"publisher":"Elsevier","page":"243-256","intvolume":"        15","date_updated":"2023-09-08T11:38:04Z","department":[{"_id":"SiHi"}],"author":[{"last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207"},{"full_name":"Sotiropoulou, Panagiota A.","first_name":"Panagiota A.","last_name":"Sotiropoulou"},{"last_name":"Heller","first_name":"Gerwin","full_name":"Heller, Gerwin"},{"last_name":"Lichtenberger","full_name":"Lichtenberger, Beate M.","first_name":"Beate M."},{"last_name":"Holcmann","first_name":"Martin","full_name":"Holcmann, Martin"},{"last_name":"Camurdanoglu","full_name":"Camurdanoglu, Bahar","first_name":"Bahar"},{"last_name":"Baykuscheva-Gentscheva","first_name":"Temenuschka","full_name":"Baykuscheva-Gentscheva, Temenuschka"},{"last_name":"Blanpain","full_name":"Blanpain, Cedric","first_name":"Cedric"},{"last_name":"Sibilia","first_name":"Maria","full_name":"Sibilia, Maria"}],"date_created":"2019-05-14T11:47:40Z","doi":"10.1016/j.isci.2019.04.018","tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"citation":{"mla":"Amberg, Nicole, et al. “EGFR Controls Hair Shaft Differentiation in a P53-Independent Manner.” <i>IScience</i>, vol. 15, Elsevier, 2019, pp. 243–56, doi:<a href=\"https://doi.org/10.1016/j.isci.2019.04.018\">10.1016/j.isci.2019.04.018</a>.","apa":"Amberg, N., Sotiropoulou, P. A., Heller, G., Lichtenberger, B. M., Holcmann, M., Camurdanoglu, B., … Sibilia, M. (2019). EGFR controls hair shaft differentiation in a p53-independent manner. <i>IScience</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.isci.2019.04.018\">https://doi.org/10.1016/j.isci.2019.04.018</a>","ista":"Amberg N, Sotiropoulou PA, Heller G, Lichtenberger BM, Holcmann M, Camurdanoglu B, Baykuscheva-Gentscheva T, Blanpain C, Sibilia M. 2019. EGFR controls hair shaft differentiation in a p53-independent manner. iScience. 15, 243–256.","ama":"Amberg N, Sotiropoulou PA, Heller G, et al. EGFR controls hair shaft differentiation in a p53-independent manner. <i>iScience</i>. 2019;15:243-256. doi:<a href=\"https://doi.org/10.1016/j.isci.2019.04.018\">10.1016/j.isci.2019.04.018</a>","short":"N. Amberg, P.A. Sotiropoulou, G. Heller, B.M. Lichtenberger, M. Holcmann, B. Camurdanoglu, T. Baykuscheva-Gentscheva, C. Blanpain, M. Sibilia, IScience 15 (2019) 243–256.","ieee":"N. Amberg <i>et al.</i>, “EGFR controls hair shaft differentiation in a p53-independent manner,” <i>iScience</i>, vol. 15. Elsevier, pp. 243–256, 2019.","chicago":"Amberg, Nicole, Panagiota A. Sotiropoulou, Gerwin Heller, Beate M. Lichtenberger, Martin Holcmann, Bahar Camurdanoglu, Temenuschka Baykuscheva-Gentscheva, Cedric Blanpain, and Maria Sibilia. “EGFR Controls Hair Shaft Differentiation in a P53-Independent Manner.” <i>IScience</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.isci.2019.04.018\">https://doi.org/10.1016/j.isci.2019.04.018</a>."},"_id":"6451","status":"public","quality_controlled":"1","has_accepted_license":"1","day":"31","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication":"iScience","article_processing_charge":"No","oa_version":"Published Version","file_date_updated":"2020-07-14T12:47:30Z","language":[{"iso":"eng"}],"date_published":"2019-05-31T00:00:00Z","year":"2019","oa":1},{"publisher":"Elsevier","page":"159-172.e7","date_updated":"2025-04-14T07:43:05Z","department":[{"_id":"SiHi"}],"intvolume":"       102","date_created":"2019-05-14T13:06:30Z","author":[{"full_name":"Ortiz-Álvarez, G","first_name":"G","last_name":"Ortiz-Álvarez"},{"last_name":"Daclin","full_name":"Daclin, M","first_name":"M"},{"last_name":"Shihavuddin","first_name":"A","full_name":"Shihavuddin, A"},{"first_name":"P","full_name":"Lansade, P","last_name":"Lansade"},{"full_name":"Fortoul, A","first_name":"A","last_name":"Fortoul"},{"full_name":"Faucourt, M","first_name":"M","last_name":"Faucourt"},{"first_name":"S","full_name":"Clavreul, S","last_name":"Clavreul"},{"last_name":"Lalioti","full_name":"Lalioti, ME","first_name":"ME"},{"last_name":"Taraviras","first_name":"S","full_name":"Taraviras, S"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"},{"last_name":"Livet","first_name":"J","full_name":"Livet, J"},{"first_name":"A","full_name":"Meunier, A","last_name":"Meunier"},{"full_name":"Genovesio, A","first_name":"A","last_name":"Genovesio"},{"full_name":"Spassky, N","first_name":"N","last_name":"Spassky"}],"doi":"10.1016/j.neuron.2019.01.051","publication_status":"published","isi":1,"issue":"1","external_id":{"pmid":["30824354"],"isi":["000463337900018"]},"ddc":["570"],"title":"Adult neural stem cells and multiciliated ependymal cells share a common lineage regulated by the Geminin family members","month":"04","publication_identifier":{"issn":["0896-6273"],"eissn":["1097-4199"]},"type":"journal_article","fulldoi":"https://doi.org/10.1016/j.neuron.2019.01.051","volume":102,"abstract":[{"text":"Adult neural stem cells and multiciliated ependymalcells are glial cells essential for neurological func-tions. Together, they make up the adult neurogenicniche. Using both high-throughput clonal analysisand single-cell resolution of progenitor division pat-terns and fate, we show that these two componentsof the neurogenic niche are lineally related: adult neu-ral stem cells are sister cells to ependymal cells,whereas most ependymal cells arise from the termi-nal symmetric divisions of the lineage. Unexpectedly,we found that the antagonist regulators of DNA repli-cation, GemC1 and Geminin, can tune the proportionof neural stem cells and ependymal cells. Our find-ings reveal the controlled dynamic of the neurogenicniche ontogeny and identify the Geminin familymembers as key regulators of the initial pool of adultneural stem cells.","lang":"eng"}],"file":[{"file_name":"2019_Neuron_Ortiz.pdf","relation":"main_file","access_level":"open_access","date_updated":"2020-07-14T12:47:30Z","content_type":"application/pdf","date_created":"2019-05-15T09:28:41Z","file_id":"6457","file_size":7288572,"checksum":"1fb6e195c583eb0c5cabf26f69ff6675","creator":"dernst"}],"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"}],"pmid":1,"language":[{"iso":"eng"}],"year":"2019","date_published":"2019-04-03T00:00:00Z","oa":1,"article_processing_charge":"No","oa_version":"Published Version","file_date_updated":"2020-07-14T12:47:30Z","has_accepted_license":"1","ec_funded":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication":"Neuron","day":"03","tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"scopus_import":"1","citation":{"ieee":"G. Ortiz-Álvarez <i>et al.</i>, “Adult neural stem cells and multiciliated ependymal cells share a common lineage regulated by the Geminin family members,” <i>Neuron</i>, vol. 102, no. 1. Elsevier, p. 159–172.e7, 2019.","chicago":"Ortiz-Álvarez, G, M Daclin, A Shihavuddin, P Lansade, A Fortoul, M Faucourt, S Clavreul, et al. “Adult Neural Stem Cells and Multiciliated Ependymal Cells Share a Common Lineage Regulated by the Geminin Family Members.” <i>Neuron</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.neuron.2019.01.051\">https://doi.org/10.1016/j.neuron.2019.01.051</a>.","short":"G. Ortiz-Álvarez, M. Daclin, A. Shihavuddin, P. Lansade, A. Fortoul, M. Faucourt, S. Clavreul, M. Lalioti, S. Taraviras, S. Hippenmeyer, J. Livet, A. Meunier, A. Genovesio, N. Spassky, Neuron 102 (2019) 159–172.e7.","apa":"Ortiz-Álvarez, G., Daclin, M., Shihavuddin, A., Lansade, P., Fortoul, A., Faucourt, M., … Spassky, N. (2019). Adult neural stem cells and multiciliated ependymal cells share a common lineage regulated by the Geminin family members. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2019.01.051\">https://doi.org/10.1016/j.neuron.2019.01.051</a>","ista":"Ortiz-Álvarez G, Daclin M, Shihavuddin A, Lansade P, Fortoul A, Faucourt M, Clavreul S, Lalioti M, Taraviras S, Hippenmeyer S, Livet J, Meunier A, Genovesio A, Spassky N. 2019. Adult neural stem cells and multiciliated ependymal cells share a common lineage regulated by the Geminin family members. Neuron. 102(1), 159–172.e7.","ama":"Ortiz-Álvarez G, Daclin M, Shihavuddin A, et al. Adult neural stem cells and multiciliated ependymal cells share a common lineage regulated by the Geminin family members. <i>Neuron</i>. 2019;102(1):159-172.e7. doi:<a href=\"https://doi.org/10.1016/j.neuron.2019.01.051\">10.1016/j.neuron.2019.01.051</a>","mla":"Ortiz-Álvarez, G., et al. “Adult Neural Stem Cells and Multiciliated Ependymal Cells Share a Common Lineage Regulated by the Geminin Family Members.” <i>Neuron</i>, vol. 102, no. 1, Elsevier, 2019, p. 159–172.e7, doi:<a href=\"https://doi.org/10.1016/j.neuron.2019.01.051\">10.1016/j.neuron.2019.01.051</a>."},"_id":"6454","status":"public","quality_controlled":"1"},{"oa_version":"Published Version","article_processing_charge":"No","date_published":"2019-05-10T00:00:00Z","year":"2019","language":[{"iso":"eng"}],"pmid":1,"oa":1,"scopus_import":"1","quality_controlled":"1","status":"public","_id":"6455","citation":{"short":"L. Telley, G. Agirman, J. Prados, N. Amberg, S. Fièvre, P. Oberst, G. Bartolini, I. Vitali, C. Cadilhac, S. Hippenmeyer, L. Nguyen, A. Dayer, D. Jabaudon, Science 364 (2019).","ieee":"L. Telley <i>et al.</i>, “Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex,” <i>Science</i>, vol. 364, no. 6440. AAAS, 2019.","chicago":"Telley, L, G Agirman, J Prados, Nicole Amberg, S Fièvre, P Oberst, G Bartolini, et al. “Temporal Patterning of Apical Progenitors and Their Daughter Neurons in the Developing Neocortex.” <i>Science</i>. AAAS, 2019. <a href=\"https://doi.org/10.1126/science.aav2522\">https://doi.org/10.1126/science.aav2522</a>.","mla":"Telley, L., et al. “Temporal Patterning of Apical Progenitors and Their Daughter Neurons in the Developing Neocortex.” <i>Science</i>, vol. 364, no. 6440, eaav2522, AAAS, 2019, doi:<a href=\"https://doi.org/10.1126/science.aav2522\">10.1126/science.aav2522</a>.","ama":"Telley L, Agirman G, Prados J, et al. Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex. <i>Science</i>. 2019;364(6440). doi:<a href=\"https://doi.org/10.1126/science.aav2522\">10.1126/science.aav2522</a>","apa":"Telley, L., Agirman, G., Prados, J., Amberg, N., Fièvre, S., Oberst, P., … Jabaudon, D. (2019). Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex. <i>Science</i>. AAAS. <a href=\"https://doi.org/10.1126/science.aav2522\">https://doi.org/10.1126/science.aav2522</a>","ista":"Telley L, Agirman G, Prados J, Amberg N, Fièvre S, Oberst P, Bartolini G, Vitali I, Cadilhac C, Hippenmeyer S, Nguyen L, Dayer A, Jabaudon D. 2019. Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex. Science. 364(6440), eaav2522."},"ec_funded":1,"article_number":"eaav2522","article_type":"original","day":"10","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Science","isi":1,"publication_status":"published","external_id":{"isi":["000467631800034"],"pmid":["31073041"]},"issue":"6440","date_created":"2019-05-14T13:07:47Z","author":[{"last_name":"Telley","first_name":"L","full_name":"Telley, L"},{"full_name":"Agirman, G","first_name":"G","last_name":"Agirman"},{"last_name":"Prados","first_name":"J","full_name":"Prados, J"},{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg"},{"full_name":"Fièvre, S","first_name":"S","last_name":"Fièvre"},{"last_name":"Oberst","first_name":"P","full_name":"Oberst, P"},{"last_name":"Bartolini","full_name":"Bartolini, G","first_name":"G"},{"last_name":"Vitali","full_name":"Vitali, I","first_name":"I"},{"first_name":"C","full_name":"Cadilhac, C","last_name":"Cadilhac"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"},{"full_name":"Nguyen, L","first_name":"L","last_name":"Nguyen"},{"first_name":"A","full_name":"Dayer, A","last_name":"Dayer"},{"last_name":"Jabaudon","first_name":"D","full_name":"Jabaudon, D"}],"intvolume":"       364","department":[{"_id":"SiHi"}],"date_updated":"2026-06-18T19:04:26Z","publisher":"AAAS","main_file_link":[{"url":"https://orbi.uliege.be/bitstream/2268/239604/1/Telley_Agirman_Science2019.pdf","open_access":"1"}],"doi":"10.1126/science.aav2522","abstract":[{"lang":"eng","text":"During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells are molecularly temporally patterned is poorly understood. We used single-cell RNA sequencing at high temporal resolution to trace the lineage of the molecular identities of successive generations of apical progenitors (APs) and their daughter neurons in mouse embryos. We identified a core set of evolutionarily conserved, temporally patterned genes that drive APs from internally driven to more exteroceptive states. We found that the Polycomb repressor complex 2 (PRC2) epigenetically regulates AP temporal progression. Embryonic age–dependent AP molecular states are transmitted to their progeny as successive ground states, onto which essentially conserved early postmitotic differentiation programs are applied, and are complemented by later-occurring environment-dependent signals. Thus, epigenetically regulated temporal molecular birthmarks present in progenitors act in their postmitotic progeny to seed adult neuronal diversity."}],"volume":364,"type":"journal_article","fulldoi":"https://doi.org/10.1126/science.aav2522","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T01031","name":"Role of Eed in neural stem cell lineage progression"}],"ddc":["570"],"publication_identifier":{"eissn":["1095-9203"],"issn":["0036-8075"]},"related_material":{"link":[{"url":"https://ist.ac.at/en/news/how-to-generate-a-brain-of-correct-size-and-composition/","relation":"press_release","description":"News on IST Homepage"}]},"month":"05","title":"Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex"},{"external_id":{"isi":["000482426800017"]},"issue":"3","isi":1,"publication_status":"published","doi":"10.1111/joa.13001","author":[{"full_name":"Picco, Noemi","first_name":"Noemi","last_name":"Picco"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Rodarte, Julio","first_name":"Julio","id":"3C70A038-F248-11E8-B48F-1D18A9856A87","last_name":"Rodarte"},{"full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen","last_name":"Streicher"},{"last_name":"Molnár","first_name":"Zoltán","full_name":"Molnár, Zoltán"},{"last_name":"Maini","first_name":"Philip K.","full_name":"Maini, Philip K."},{"last_name":"Woolley","full_name":"Woolley, Thomas E.","first_name":"Thomas E."}],"date_created":"2019-09-02T11:57:28Z","date_updated":"2025-04-14T07:43:05Z","department":[{"_id":"SiHi"}],"intvolume":"       235","page":"686-696","publisher":"Wiley","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"file":[{"date_created":"2019-09-02T12:05:18Z","content_type":"application/pdf","date_updated":"2020-07-14T12:47:42Z","access_level":"open_access","relation":"main_file","file_name":"2019_JournalAnatomy_Picco.pdf","creator":"dernst","checksum":"160f960844b204057f20896e0e1f8ee7","file_id":"6845","file_size":1192994}],"abstract":[{"text":"Studying the progression of the proliferative and differentiative patterns of neural stem cells at the individual cell level is crucial to the understanding of cortex development and how the disruption of such patterns can lead to malformations and neurodevelopmental diseases. However, our understanding of the precise lineage progression programme at single-cell resolution is still incomplete due to the technical variations in lineage- tracing approaches. One of the key challenges involves developing a robust theoretical framework in which we can integrate experimental observations and introduce correction factors to obtain a reliable and representative description of the temporal modulation of proliferation and differentiation. In order to obtain more conclusive insights, we carry out virtual clonal analysis using mathematical modelling and compare our results against experimental data. Using a dataset obtained with Mosaic Analysis with Double Markers, we illustrate how the theoretical description can be exploited to interpret and reconcile the disparity between virtual and experimental results.","lang":"eng"}],"volume":235,"fulldoi":"https://doi.org/10.1111/joa.13001","type":"journal_article","license":"https://creativecommons.org/licenses/by-nc/4.0/","publication_identifier":{"issn":["0021-8782"],"eissn":["1469-7580"]},"month":"09","title":"A mathematical insight into cell labelling experiments for clonal analysis","ddc":["570"],"file_date_updated":"2020-07-14T12:47:42Z","oa_version":"Published Version","article_processing_charge":"No","oa":1,"date_published":"2019-09-01T00:00:00Z","year":"2019","language":[{"iso":"eng"}],"quality_controlled":"1","status":"public","_id":"6844","citation":{"mla":"Picco, Noemi, et al. “A Mathematical Insight into Cell Labelling Experiments for Clonal Analysis.” <i>Journal of Anatomy</i>, vol. 235, no. 3, Wiley, 2019, pp. 686–96, doi:<a href=\"https://doi.org/10.1111/joa.13001\">10.1111/joa.13001</a>.","ista":"Picco N, Hippenmeyer S, Rodarte J, Streicher C, Molnár Z, Maini PK, Woolley TE. 2019. A mathematical insight into cell labelling experiments for clonal analysis. Journal of Anatomy. 235(3), 686–696.","apa":"Picco, N., Hippenmeyer, S., Rodarte, J., Streicher, C., Molnár, Z., Maini, P. K., &#38; Woolley, T. E. (2019). A mathematical insight into cell labelling experiments for clonal analysis. <i>Journal of Anatomy</i>. Wiley. <a href=\"https://doi.org/10.1111/joa.13001\">https://doi.org/10.1111/joa.13001</a>","ama":"Picco N, Hippenmeyer S, Rodarte J, et al. A mathematical insight into cell labelling experiments for clonal analysis. <i>Journal of Anatomy</i>. 2019;235(3):686-696. doi:<a href=\"https://doi.org/10.1111/joa.13001\">10.1111/joa.13001</a>","short":"N. Picco, S. Hippenmeyer, J. Rodarte, C. Streicher, Z. Molnár, P.K. Maini, T.E. Woolley, Journal of Anatomy 235 (2019) 686–696.","chicago":"Picco, Noemi, Simon Hippenmeyer, Julio Rodarte, Carmen Streicher, Zoltán Molnár, Philip K. Maini, and Thomas E. Woolley. “A Mathematical Insight into Cell Labelling Experiments for Clonal Analysis.” <i>Journal of Anatomy</i>. Wiley, 2019. <a href=\"https://doi.org/10.1111/joa.13001\">https://doi.org/10.1111/joa.13001</a>.","ieee":"N. Picco <i>et al.</i>, “A mathematical insight into cell labelling experiments for clonal analysis,” <i>Journal of Anatomy</i>, vol. 235, no. 3. Wiley, pp. 686–696, 2019."},"scopus_import":"1","tmp":{"image":"/images/cc_by_nc.png","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"publication":"Journal of Anatomy","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_type":"original","day":"01","ec_funded":1,"has_accepted_license":"1"},{"file":[{"creator":"dernst","file_size":4334962,"file_id":"7452","checksum":"ec1fb2aebb874009bc309adaada6e1d7","access_level":"open_access","date_created":"2020-02-05T10:30:02Z","date_updated":"2020-07-14T12:47:47Z","content_type":"application/pdf","file_name":"2019_JournNeurochemistry_Cheung.pdf","relation":"main_file"}],"fulldoi":"https://doi.org/10.1111/jnc.14862","type":"journal_article","abstract":[{"lang":"eng","text":"Activity-dependent bulk endocytosis generates synaptic vesicles (SVs) during intense neuronal activity via a two-step process. First, bulk endosomes are formed direct from the plasma membrane from which SVs are then generated. SV generation from bulk endosomes requires the efflux of previously accumulated calcium and activation of the protein phosphatase calcineurin. However, it is still unknown how calcineurin mediates SV generation. We addressed this question using a series of acute interventions that decoupled the generation of SVs from bulk endosomes in rat primary neuronal culture. This was achieved by either disruption of protein–protein interactions via delivery of competitive peptides, or inhibition of enzyme activity by known inhibitors. SV generation was monitored using either a morphological horseradish peroxidase assay or an optical assay that monitors the replenishment of the reserve SV pool. We found that SV generation was inhibited by, (i) peptides that disrupt calcineurin interactions, (ii) an inhibitor of dynamin I GTPase activity and (iii) peptides that disrupt the phosphorylation-dependent dynamin I–syndapin I interaction. Peptides that disrupted syndapin I interactions with eps15 homology domain-containing proteins had no effect. This revealed that (i) calcineurin must be localized at bulk endosomes to mediate its effect, (ii) dynamin I GTPase activity is essential for SV fission and (iii) the calcineurin-dependent interaction between dynamin I and syndapin I is essential for SV generation. We therefore propose that a calcineurin-dependent dephosphorylation cascade that requires both dynamin I GTPase and syndapin I lipid-deforming activity is essential for SV generation from bulk endosomes."}],"volume":151,"publication_identifier":{"eissn":["1471-4159"],"issn":["0022-3042"]},"title":"Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction","month":"12","ddc":["570"],"issue":"5","external_id":{"pmid":["31479508"],"isi":["000490703100001"]},"isi":1,"publication_status":"published","doi":"10.1111/jnc.14862","intvolume":"       151","department":[{"_id":"SiHi"}],"date_updated":"2023-08-30T07:21:50Z","author":[{"last_name":"Cheung","first_name":"Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572"},{"full_name":"Cousin, Michael A.","first_name":"Michael A.","last_name":"Cousin"}],"date_created":"2019-11-12T14:37:08Z","publisher":"Wiley","page":"570-583","status":"public","quality_controlled":"1","citation":{"chicago":"Cheung, Giselle T, and Michael A. Cousin. “Synaptic Vesicle Generation from Activity‐dependent Bulk Endosomes Requires a Dephosphorylation‐dependent Dynamin–Syndapin Interaction.” <i>Journal of Neurochemistry</i>. Wiley, 2019. <a href=\"https://doi.org/10.1111/jnc.14862\">https://doi.org/10.1111/jnc.14862</a>.","ieee":"G. T. Cheung and M. A. Cousin, “Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction,” <i>Journal of Neurochemistry</i>, vol. 151, no. 5. Wiley, pp. 570–583, 2019.","short":"G.T. Cheung, M.A. Cousin, Journal of Neurochemistry 151 (2019) 570–583.","ista":"Cheung GT, Cousin MA. 2019. Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction. Journal of Neurochemistry. 151(5), 570–583.","apa":"Cheung, G. T., &#38; Cousin, M. A. (2019). Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction. <i>Journal of Neurochemistry</i>. Wiley. <a href=\"https://doi.org/10.1111/jnc.14862\">https://doi.org/10.1111/jnc.14862</a>","ama":"Cheung GT, Cousin MA. Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction. <i>Journal of Neurochemistry</i>. 2019;151(5):570-583. doi:<a href=\"https://doi.org/10.1111/jnc.14862\">10.1111/jnc.14862</a>","mla":"Cheung, Giselle T., and Michael A. Cousin. “Synaptic Vesicle Generation from Activity‐dependent Bulk Endosomes Requires a Dephosphorylation‐dependent Dynamin–Syndapin Interaction.” <i>Journal of Neurochemistry</i>, vol. 151, no. 5, Wiley, 2019, pp. 570–83, doi:<a href=\"https://doi.org/10.1111/jnc.14862\">10.1111/jnc.14862</a>."},"_id":"7005","scopus_import":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"day":"01","article_type":"original","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication":"Journal of Neurochemistry","has_accepted_license":"1","file_date_updated":"2020-07-14T12:47:47Z","article_processing_charge":"No","oa_version":"Published Version","oa":1,"pmid":1,"language":[{"iso":"eng"}],"year":"2019","date_published":"2019-12-01T00:00:00Z"},{"abstract":[{"text":"The cerebral cortex contains multiple areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modelling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas.","lang":"eng"}],"volume":8,"fulldoi":"https://doi.org/10.7554/eLife.51381","type":"journal_article","project":[{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"},{"_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"}],"file":[{"creator":"dernst","file_id":"7503","file_size":2960543,"checksum":"b460ecc33e1a68265e7adea775021f3a","access_level":"open_access","date_created":"2020-02-18T15:19:26Z","date_updated":"2020-07-14T12:47:53Z","content_type":"application/pdf","file_name":"2019_eLife_Llorca.pdf","relation":"main_file"}],"ddc":["570"],"month":"11","title":"A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture","publication_identifier":{"eissn":["2050-084X"]},"publication_status":"published","isi":1,"external_id":{"pmid":["31736464"],"isi":["000508156800001"]},"publisher":"eLife Sciences Publications","author":[{"first_name":"Alfredo","full_name":"Llorca, Alfredo","last_name":"Llorca"},{"first_name":"Gabriele","full_name":"Ciceri, Gabriele","last_name":"Ciceri"},{"last_name":"Beattie","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753"},{"full_name":"Wong, Fong Kuan","first_name":"Fong Kuan","last_name":"Wong"},{"last_name":"Diana","first_name":"Giovanni","full_name":"Diana, Giovanni"},{"full_name":"Serafeimidou-Pouliou, Eleni","first_name":"Eleni","last_name":"Serafeimidou-Pouliou"},{"full_name":"Fernández-Otero, Marian","first_name":"Marian","last_name":"Fernández-Otero"},{"last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen","full_name":"Streicher, Carmen"},{"last_name":"Arnold","first_name":"Sebastian J.","full_name":"Arnold, Sebastian J."},{"full_name":"Meyer, Martin","first_name":"Martin","last_name":"Meyer"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer"},{"first_name":"Miguel","full_name":"Maravall, Miguel","last_name":"Maravall"},{"last_name":"Marín","first_name":"Oscar","full_name":"Marín, Oscar"}],"date_created":"2019-12-22T23:00:42Z","date_updated":"2026-04-03T09:46:33Z","intvolume":"         8","department":[{"_id":"SiHi"}],"doi":"10.7554/eLife.51381","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"scopus_import":"1","_id":"7202","citation":{"chicago":"Llorca, Alfredo, Gabriele Ciceri, Robert J Beattie, Fong Kuan Wong, Giovanni Diana, Eleni Serafeimidou-Pouliou, Marian Fernández-Otero, et al. “A Stochastic Framework of Neurogenesis Underlies the Assembly of Neocortical Cytoarchitecture.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.51381\">https://doi.org/10.7554/eLife.51381</a>.","ieee":"A. Llorca <i>et al.</i>, “A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","short":"A. Llorca, G. Ciceri, R.J. Beattie, F.K. Wong, G. Diana, E. Serafeimidou-Pouliou, M. Fernández-Otero, C. Streicher, S.J. Arnold, M. Meyer, S. Hippenmeyer, M. Maravall, O. Marín, ELife 8 (2019).","ama":"Llorca A, Ciceri G, Beattie RJ, et al. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.51381\">10.7554/eLife.51381</a>","apa":"Llorca, A., Ciceri, G., Beattie, R. J., Wong, F. K., Diana, G., Serafeimidou-Pouliou, E., … Marín, O. (2019). A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.51381\">https://doi.org/10.7554/eLife.51381</a>","ista":"Llorca A, Ciceri G, Beattie RJ, Wong FK, Diana G, Serafeimidou-Pouliou E, Fernández-Otero M, Streicher C, Arnold SJ, Meyer M, Hippenmeyer S, Maravall M, Marín O. 2019. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. eLife. 8, e51381.","mla":"Llorca, Alfredo, et al. “A Stochastic Framework of Neurogenesis Underlies the Assembly of Neocortical Cytoarchitecture.” <i>ELife</i>, vol. 8, e51381, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.51381\">10.7554/eLife.51381</a>."},"quality_controlled":"1","status":"public","ec_funded":1,"article_number":"e51381","has_accepted_license":"1","publication":"eLife","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","article_type":"original","day":"18","oa_version":"Published Version","article_processing_charge":"No","file_date_updated":"2020-07-14T12:47:53Z","date_published":"2019-11-18T00:00:00Z","year":"2019","pmid":1,"language":[{"iso":"eng"}],"oa":1}]