[{"acknowledgement":"We thank Florian Pauler for discussion and his expert technical support. This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging and Optics Facility (IOF) and Preclinical Facility (PCF). A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences.","publisher":"Elsevier","quality_controlled":"1","oa":1,"day":"01","publication":"STAR Protocols","year":"2024","doi":"10.1016/j.xpro.2023.102795","date_published":"2024-01-01T00:00:00Z","date_created":"2024-01-14T23:00:56Z","article_number":"102795","project":[{"name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Hansen AH, Hippenmeyer S. 2024. Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. STAR Protocols. 5(1), 102795.","chicago":"Hansen, Andi H, and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols. Elsevier, 2024. https://doi.org/10.1016/j.xpro.2023.102795.","short":"A.H. Hansen, S. Hippenmeyer, STAR Protocols 5 (2024).","ieee":"A. H. Hansen and S. Hippenmeyer, “Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers,” STAR Protocols, vol. 5, no. 1. Elsevier, 2024.","apa":"Hansen, A. H., & Hippenmeyer, S. (2024). Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2023.102795","ama":"Hansen AH, Hippenmeyer S. Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers. STAR Protocols. 2024;5(1). doi:10.1016/j.xpro.2023.102795","mla":"Hansen, Andi H., and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols, vol. 5, no. 1, 102795, Elsevier, 2024, doi:10.1016/j.xpro.2023.102795."},"title":"Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers","author":[{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","full_name":"Hansen, Andi H","last_name":"Hansen"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"external_id":{"pmid":["38165800"]},"article_processing_charge":"Yes","oa_version":"Published Version","pmid":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"abstract":[{"text":"Mosaic analysis with double markers (MADM) technology enables the sparse labeling of genetically defined neurons. We present a protocol for time-lapse imaging of cortical projection neuron migration in mice using MADM. We describe steps for the isolation, culturing, and 4D imaging of neuronal dynamics in MADM-labeled brain tissue. While this protocol is compatible with other single-cell labeling methods, the MADM approach provides a genetic platform for the functional assessment of cell-autonomous candidate gene function and the relative contribution of non-cell-autonomous effects.\r\n\r\nFor complete details on the use and execution of this protocol, please refer to Hansen et al. (2022),1 Contreras et al. (2021),2 and Amberg and Hippenmeyer (2021).3","lang":"eng"}],"month":"01","intvolume":" 5","scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1016/j.xpro.2023.102795","open_access":"1"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2666-1667"]},"publication_status":"epub_ahead","issue":"1","volume":5,"related_material":{"link":[{"relation":"software","url":"http://github.com/hippenmeyerlab"}]},"_id":"14794","status":"public","article_type":"review","type":"journal_article","date_updated":"2024-01-17T10:32:31Z","department":[{"_id":"SiHi"}]},{"publication_identifier":{"eissn":["2753-149X"]},"publication_status":"published","file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"file_id":"14061","checksum":"822e76e056c07099d1fb27d1ece5941b","file_size":4846551,"date_updated":"2023-08-16T08:00:30Z","creator":"dernst","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","date_created":"2023-08-16T08:00:30Z"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12726"},{"relation":"dissertation_contains","status":"public","id":"14530"}]},"issue":"1","volume":1,"ec_funded":1,"abstract":[{"text":"The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general.","lang":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"oa_version":"Published Version","month":"07","intvolume":" 1","date_updated":"2023-11-30T10:55:12Z","ddc":["570"],"department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"file_date_updated":"2023-08-16T08:00:30Z","_id":"10791","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","has_accepted_license":"1","year":"2022","day":"07","publication":"Oxford Open Neuroscience","date_published":"2022-07-07T00:00:00Z","doi":"10.1093/oons/kvac009","date_created":"2022-02-25T07:52:11Z","acknowledgement":"A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility.","publisher":"Oxford Academic","quality_controlled":"1","oa":1,"citation":{"mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009, Oxford Academic, 2022, doi:10.1093/oons/kvac009.","apa":"Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. Oxford Academic. https://doi.org/10.1093/oons/kvac009","ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1). doi:10.1093/oons/kvac009","short":"A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022).","ieee":"A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” Oxford Open Neuroscience, vol. 1, no. 1. Oxford Academic, 2022.","chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience. Oxford Academic, 2022. https://doi.org/10.1093/oons/kvac009.","ista":"Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","full_name":"Hansen, Andi H"},{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler"},{"last_name":"Riedl","orcid":"0000-0003-4844-6311","full_name":"Riedl, Michael","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena","full_name":"Heger, Anna-Magdalena","last_name":"Heger"},{"first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","last_name":"Laukoter"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Nicolas, Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel"},{"full_name":"Hof, Björn","orcid":"0000-0003-2057-2754","last_name":"Hof","id":"3A374330-F248-11E8-B48F-1D18A9856A87","first_name":"Björn"},{"first_name":"Li Huei","last_name":"Tsai","full_name":"Tsai, Li Huei"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"}],"article_processing_charge":"No","title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","article_number":"kvac009","project":[{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444"},{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812"}]},{"abstract":[{"text":"Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated are unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, while intermediate levels of Notch activity generate inhibitory neurons, and daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","intvolume":" 35","month":"06","publication_status":"published","publication_identifier":{"eissn":[" 22111247"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"checksum":"7def3d42ebc8f5675efb6f38819e3e2e","file_id":"9554","file_size":8900385,"date_updated":"2021-06-15T14:01:35Z","creator":"cziletti","file_name":"2021_CellReports_Zhang.pdf","date_created":"2021-06-15T14:01:35Z"}],"ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","volume":35,"related_material":{"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.03.18.997205"}]},"issue":"10","_id":"8546","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","article_type":"original","status":"public","date_updated":"2023-08-04T11:00:48Z","ddc":["570"],"file_date_updated":"2021-06-15T14:01:35Z","department":[{"_id":"SiHi"}],"acknowledgement":"This work was supported by the program “Investissements d’avenir” ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under the European Union’s Horizon 2020 research and innovation programme grant agreement no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.” Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant, and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility, iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2 mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies. B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .","oa":1,"publisher":"Elsevier","quality_controlled":"1","year":"2021","isi":1,"has_accepted_license":"1","publication":"Cell Reports","day":"08","date_created":"2020-09-21T12:00:48Z","date_published":"2021-06-08T00:00:00Z","doi":"10.1016/j.celrep.2021.109208","article_number":"109208","project":[{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"citation":{"mla":"Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” Cell Reports, vol. 35, no. 10, 109208, Elsevier, 2021, doi:10.1016/j.celrep.2021.109208.","short":"T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen, C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell Reports 35 (2021).","ieee":"T. Zhang et al., “Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum,” Cell Reports, vol. 35, no. 10. Elsevier, 2021.","apa":"Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan, B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109208","ama":"Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. 2021;35(10). doi:10.1016/j.celrep.2021.109208","chicago":"Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand, Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” Cell Reports. Elsevier, 2021. https://doi.org/10.1016/j.celrep.2021.109208.","ista":"Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. 35(10), 109208."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"pmid":["34107249 "],"isi":["000659894300001"]},"author":[{"first_name":"Tingting","full_name":"Zhang, Tingting","last_name":"Zhang"},{"first_name":"Tengyuan","last_name":"Liu","full_name":"Liu, Tengyuan"},{"full_name":"Mora, Natalia","last_name":"Mora","first_name":"Natalia"},{"last_name":"Guegan","full_name":"Guegan, Justine","first_name":"Justine"},{"last_name":"Bertrand","full_name":"Bertrand, Mathilde","first_name":"Mathilde"},{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","first_name":"Ximena","full_name":"Contreras, Ximena","last_name":"Contreras"},{"last_name":"Hansen","full_name":"Hansen, Andi H","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Streicher","full_name":"Streicher, Carmen","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Marica","full_name":"Anderle, Marica","last_name":"Anderle"},{"last_name":"Danda","full_name":"Danda, Natasha","first_name":"Natasha"},{"full_name":"Tiberi, Luca","last_name":"Tiberi","first_name":"Luca"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"full_name":"Hassan, Bassem A.","last_name":"Hassan","first_name":"Bassem A."}],"title":"Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum"},{"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"intvolume":" 35","month":"06","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"file_id":"9613","checksum":"d49520fdcbbb5c2f883bddb67cee5d77","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2021-06-28T14:06:24Z","file_name":"2021_CellReports_Contreras.pdf","creator":"asandaue","date_updated":"2021-06-28T14:06:24Z","file_size":7653149}],"publication_status":"published","publication_identifier":{"eissn":["22111247"]},"ec_funded":1,"volume":35,"issue":"12","related_material":{"link":[{"url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/","relation":"press_release","description":"News on IST Homepage"}]},"_id":"9603","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"article_type":"original","type":"journal_article","ddc":["570"],"date_updated":"2023-08-10T13:55:00Z","department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"file_date_updated":"2021-06-28T14:06:24Z","acknowledgement":"We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 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.","oa":1,"publisher":"Cell Press","quality_controlled":"1","publication":"Cell Reports","day":"22","year":"2021","isi":1,"has_accepted_license":"1","date_created":"2021-06-27T22:01:48Z","doi":"10.1016/j.celrep.2021.109274","date_published":"2021-06-22T00:00:00Z","article_number":"109274","project":[{"name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274.","chicago":"Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports. Cell Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.","apa":"Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274","ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12). doi:10.1016/j.celrep.2021.109274","short":"X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen, T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo, T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).","ieee":"X. Contreras et al., “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021.","mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press, 2021, doi:10.1016/j.celrep.2021.109274."},"title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis","article_processing_charge":"No","external_id":{"isi":["000664463600016"]},"author":[{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","first_name":"Ximena","last_name":"Contreras","full_name":"Contreras, Ximena"},{"last_name":"Amberg","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Davaatseren, Amarbayasgalan","last_name":"Davaatseren","id":"70ADC922-B424-11E9-99E3-BA18E6697425","first_name":"Amarbayasgalan"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","full_name":"Hansen, Andi H","last_name":"Hansen"},{"full_name":"Sonntag, Johanna","last_name":"Sonntag","id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87","first_name":"Johanna"},{"first_name":"Lill","full_name":"Andersen, Lill","last_name":"Andersen"},{"first_name":"Tina","full_name":"Bernthaler, Tina","last_name":"Bernthaler"},{"last_name":"Streicher","full_name":"Streicher, Carmen","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena","last_name":"Heger","full_name":"Heger, Anna-Magdalena"},{"last_name":"Johnson","full_name":"Johnson, Randy L.","first_name":"Randy L."},{"last_name":"Schwarz","full_name":"Schwarz, Lindsay A.","first_name":"Lindsay A."},{"first_name":"Liqun","last_name":"Luo","full_name":"Luo, Liqun"},{"full_name":"Rülicke, Thomas","last_name":"Rülicke","first_name":"Thomas"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"}]},{"doi":"10.15479/at:ista:9962","date_published":"2021-09-02T00:00:00Z","date_created":"2021-08-29T12:36:50Z","page":"182","day":"02","has_accepted_license":"1","year":"2021","publisher":"Institute of Science and Technology Austria","oa":1,"title":"Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration","author":[{"full_name":"Hansen, Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Hansen, Andi H. Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:9962.","apa":"Hansen, A. H. (2021). Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:9962","ama":"Hansen AH. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. 2021. doi:10.15479/at:ista:9962","short":"A.H. Hansen, Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration, Institute of Science and Technology Austria, 2021.","ieee":"A. H. Hansen, “Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration,” Institute of Science and Technology Austria, 2021.","chicago":"Hansen, Andi H. “Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:9962.","ista":"Hansen AH. 2021. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. Institute of Science and Technology Austria."},"project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812"}],"related_material":{"record":[{"relation":"part_of_dissertation","id":"8569","status":"public"},{"relation":"part_of_dissertation","id":"960","status":"public"}]},"file":[{"file_id":"9971","checksum":"66b56f5b988b233dc66a4f4b4fb2cdfe","relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"Thesis_Hansen.docx","date_created":"2021-08-30T09:17:39Z","creator":"ahansen","file_size":10629190,"date_updated":"2022-09-03T22:30:04Z"},{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","embargo":"2022-09-02","checksum":"204fa40321a1c6289b68c473634c4bf3","file_id":"9972","creator":"ahansen","file_size":13457469,"date_updated":"2022-09-03T22:30:04Z","file_name":"Thesis_Hansen_PDFA-1a.pdf","date_created":"2021-08-30T09:29:44Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","month":"09","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"text":"The brain is one of the largest and most complex organs and it is composed of billions of neurons that communicate together enabling e.g. consciousness. The cerebral cortex is the largest site of neural integration in the central nervous system. Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final position, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at certain steps during the overall migration process. Moreover, functional analysis of genetic mosaics (mutant neurons present in wild-type/heterozygote environment) using the MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. The interactions of cell-intrinsic (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely unknown. In part of this thesis work we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-cell-autonomous and/or community effects. The direct comparison of mutant neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively analyze non-cell-autonomous effects. Such analysis enable the high-resolution analysis of projection neuron migration dynamics in distinct environments with concomitant isolation of genomic and proteomic profiles. Using these experimental paradigms and in combination with computational modeling we show and characterize the nature of non-cell-autonomous effects to coordinate radial neuron migration. Furthermore, this thesis discusses recent developments in neurodevelopment with focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal migration.","lang":"eng"}],"department":[{"_id":"GradSch"},{"_id":"SiHi"}],"file_date_updated":"2022-09-03T22:30:04Z","ddc":["570"],"supervisor":[{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"}],"date_updated":"2023-09-22T09:58:30Z","status":"public","keyword":["Neuronal migration","Non-cell-autonomous","Cell-autonomous","Neurodevelopmental disease"],"type":"dissertation","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"9962"},{"year":"2020","has_accepted_license":"1","isi":1,"publication":"Neuron","day":"23","page":"1160-1179.e9","date_created":"2020-07-23T16:03:12Z","date_published":"2020-09-23T00:00:00Z","doi":"10.1016/j.neuron.2020.06.031","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.","oa":1,"quality_controlled":"1","publisher":"Elsevier","citation":{"ieee":"S. Laukoter et al., “Cell-type specificity of genomic imprinting in cerebral cortex,” Neuron, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.","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.","apa":"Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher, C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.06.031","ama":"Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 2020;107(6):1160-1179.e9. doi:10.1016/j.neuron.2020.06.031","mla":"Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:10.1016/j.neuron.2020.06.031.","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.","chicago":"Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.06.031."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"isi":["000579698700006"]},"author":[{"full_name":"Laukoter, Susanne","orcid":"0000-0002-7903-3010","last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne"},{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048"},{"id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","last_name":"Beattie","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753"},{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","full_name":"Hansen, Andi H","last_name":"Hansen"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen","last_name":"Streicher","full_name":"Streicher, Carmen"},{"first_name":"Thomas","full_name":"Penz, Thomas","last_name":"Penz"},{"first_name":"Christoph","last_name":"Bock","full_name":"Bock, Christoph","orcid":"0000-0001-6091-3088"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"title":"Cell-type specificity of genomic imprinting in cerebral cortex","project":[{"grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"},{"name":"Role of Eed in neural stem cell lineage progression","grant_number":"T0101031","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex"},{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425"},{"name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014","_id":"25D7962E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"publication_status":"published","publication_identifier":{"issn":["0896-6273"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2020-12-02T09:26:46Z","file_name":"2020_Neuron_Laukoter.pdf","date_updated":"2020-12-02T09:26:46Z","file_size":8911830,"creator":"dernst","file_id":"8828","checksum":"7becdc16a6317304304631087ae7dd7f","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"ec_funded":1,"issue":"6","volume":107,"related_material":{"link":[{"description":"News on IST Website","url":"https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/","relation":"press_release"}]},"abstract":[{"lang":"eng","text":"In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"oa_version":"Published Version","scopus_import":"1","intvolume":" 107","month":"09","date_updated":"2023-08-22T08:20:11Z","ddc":["570"],"file_date_updated":"2020-12-02T09:26:46Z","department":[{"_id":"SiHi"}],"_id":"8162","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","article_type":"original","status":"public"},{"ddc":["570"],"date_updated":"2024-03-27T23:30:40Z","file_date_updated":"2020-09-28T13:11:17Z","department":[{"_id":"SiHi"}],"_id":"8569","status":"public","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file":[{"file_name":"2020_Frontiers_Hansen.pdf","date_created":"2020-09-28T13:11:17Z","creator":"dernst","file_size":5527139,"date_updated":"2020-09-28T13:11:17Z","success":1,"file_id":"8584","checksum":"01f731824194c94c81a5da360d997073","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2296-634X"]},"publication_status":"published","volume":8,"issue":"9","related_material":{"record":[{"relation":"dissertation_contains","id":"9962","status":"public"}]},"ec_funded":1,"oa_version":"Published Version","pmid":1,"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."}],"month":"09","intvolume":" 8","scopus_import":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Hansen, Andi H., and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” Frontiers in Cell and Developmental Biology, vol. 8, no. 9, 574382, Frontiers, 2020, doi:10.3389/fcell.2020.574382.","ieee":"A. H. Hansen and S. Hippenmeyer, “Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex,” Frontiers in Cell and Developmental Biology, vol. 8, no. 9. Frontiers, 2020.","short":"A.H. Hansen, S. Hippenmeyer, Frontiers in Cell and Developmental Biology 8 (2020).","ama":"Hansen AH, Hippenmeyer S. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. 2020;8(9). doi:10.3389/fcell.2020.574382","apa":"Hansen, A. H., & Hippenmeyer, S. (2020). Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. Frontiers. https://doi.org/10.3389/fcell.2020.574382","chicago":"Hansen, Andi H, and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” Frontiers in Cell and Developmental Biology. Frontiers, 2020. https://doi.org/10.3389/fcell.2020.574382.","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."},"title":"Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex","author":[{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","full_name":"Hansen, Andi H","last_name":"Hansen"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"article_processing_charge":"Yes (via OA deal)","external_id":{"isi":["000577915900001"],"pmid":["33102480"]},"article_number":"574382","project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"}],"day":"25","publication":"Frontiers in Cell and Developmental Biology","has_accepted_license":"1","isi":1,"year":"2020","date_published":"2020-09-25T00:00:00Z","doi":"10.3389/fcell.2020.574382","date_created":"2020-09-26T06:11:07Z","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.","quality_controlled":"1","publisher":"Frontiers","oa":1},{"scopus_import":"1","month":"05","abstract":[{"lang":"eng","text":"Beginning from a limited pool of progenitors, the mammalian cerebral cortex forms highly organized functional neural circuits. However, the underlying cellular and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs) and eventual production of neurons and glia in the developing neuroepithelium remains unclear. Methods to trace NSC division patterns and map the lineage of clonally related cells have advanced dramatically. However, many contemporary lineage tracing techniques suffer from the lack of cellular resolution of progeny cell fate, which is essential for deciphering progenitor cell division patterns. Presented is a protocol using mosaic analysis with double markers (MADM) to perform in vivo clonal analysis. MADM concomitantly manipulates individual progenitor cells and visualizes precise division patterns and lineage progression at unprecedented single cell resolution. MADM-based interchromosomal recombination events during the G2-X phase of mitosis, together with temporally inducible CreERT2, provide exact information on the birth dates of clones and their division patterns. Thus, MADM lineage tracing provides unprecedented qualitative and quantitative optical readouts of the proliferation mode of stem cell progenitors at the single cell level. MADM also allows for examination of the mechanisms and functional requirements of candidate genes in NSC lineage progression. This method is unique in that comparative analysis of control and mutant subclones can be performed in the same tissue environment in vivo. Here, the protocol is described in detail, and experimental paradigms to employ MADM for clonal analysis and lineage tracing in the developing cerebral cortex are demonstrated. Importantly, this protocol can be adapted to perform MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver is present."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"oa_version":"Published Version","related_material":{"record":[{"id":"7902","status":"public","relation":"part_of_dissertation"}]},"issue":"159","ec_funded":1,"publication_identifier":{"issn":["1940-087X"]},"publication_status":"published","file":[{"file_name":"jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf","date_created":"2020-05-11T08:28:38Z","file_size":1352186,"date_updated":"2020-07-14T12:48:03Z","creator":"rbeattie","checksum":"3154ea7f90b9fb45e084cd1c2770597d","file_id":"7816","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","_id":"7815","file_date_updated":"2020-07-14T12:48:03Z","department":[{"_id":"SiHi"}],"date_updated":"2024-03-27T23:30:41Z","ddc":["570"],"quality_controlled":"1","publisher":"MyJove Corporation","oa":1,"doi":"10.3791/61147","date_published":"2020-05-08T00:00:00Z","date_created":"2020-05-11T08:31:20Z","has_accepted_license":"1","isi":1,"year":"2020","day":"08","publication":"Journal of Visual Experiments","project":[{"call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex"},{"grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"article_number":"e61147","author":[{"last_name":"Beattie","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J"},{"first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","full_name":"Streicher, Carmen"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","last_name":"Amberg","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207"},{"id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T","full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572","last_name":"Cheung"},{"full_name":"Contreras, Ximena","last_name":"Contreras","first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hansen","full_name":"Hansen, Andi H","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000546406600043"]},"article_processing_charge":"No","title":"Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM)","citation":{"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.","chicago":"Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal of Visual Experiments. MyJove Corporation, 2020. https://doi.org/10.3791/61147.","apa":"Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen, A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147","ama":"Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. 2020;(159). doi:10.3791/61147","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 et al., “Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM),” Journal of Visual Experiments, no. 159. MyJove Corporation, 2020.","mla":"Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal of Visual Experiments, no. 159, e61147, MyJove Corporation, 2020, doi:10.3791/61147."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"author":[{"full_name":"Gstrein, Thomas","last_name":"Gstrein","first_name":"Thomas"},{"first_name":"Andrew","last_name":"Edwards","full_name":"Edwards, Andrew"},{"first_name":"Anna","full_name":"Přistoupilová, Anna","last_name":"Přistoupilová"},{"first_name":"Ines","last_name":"Leca","full_name":"Leca, Ines"},{"last_name":"Breuss","full_name":"Breuss, Martin","first_name":"Martin"},{"first_name":"Sandra","full_name":"Pilat Carotta, Sandra","last_name":"Pilat Carotta"},{"first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","full_name":"Hansen, Andi H"},{"first_name":"Ratna","full_name":"Tripathy, Ratna","last_name":"Tripathy"},{"first_name":"Anna","last_name":"Traunbauer","full_name":"Traunbauer, Anna"},{"full_name":"Hochstoeger, Tobias","last_name":"Hochstoeger","first_name":"Tobias"},{"first_name":"Gavril","full_name":"Rosoklija, Gavril","last_name":"Rosoklija"},{"first_name":"Marco","last_name":"Repic","full_name":"Repic, Marco"},{"first_name":"Lukas","last_name":"Landler","full_name":"Landler, Lukas"},{"first_name":"Viktor","last_name":"Stránecký","full_name":"Stránecký, Viktor"},{"last_name":"Dürnberger","full_name":"Dürnberger, Gerhard","first_name":"Gerhard"},{"first_name":"Thomas","last_name":"Keane","full_name":"Keane, Thomas"},{"first_name":"Johannes","full_name":"Zuber, Johannes","last_name":"Zuber"},{"full_name":"Adams, David","last_name":"Adams","first_name":"David"},{"full_name":"Flint, Jonathan","last_name":"Flint","first_name":"Jonathan"},{"first_name":"Tomas","full_name":"Honzik, Tomas","last_name":"Honzik"},{"first_name":"Marta","last_name":"Gut","full_name":"Gut, Marta"},{"first_name":"Sergi","full_name":"Beltran, Sergi","last_name":"Beltran"},{"first_name":"Karl","full_name":"Mechtler, Karl","last_name":"Mechtler"},{"first_name":"Elliott","full_name":"Sherr, Elliott","last_name":"Sherr"},{"first_name":"Stanislav","full_name":"Kmoch, Stanislav","last_name":"Kmoch"},{"first_name":"Ivo","last_name":"Gut","full_name":"Gut, Ivo"},{"first_name":"David","last_name":"Keays","full_name":"Keays, David"}],"publist_id":"7267","external_id":{"isi":["000424269900012"]},"article_processing_charge":"No","title":"Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans","citation":{"ista":"Gstrein T, Edwards A, Přistoupilová A, Leca I, Breuss M, Pilat Carotta S, Hansen AH, Tripathy R, Traunbauer A, Hochstoeger T, Rosoklija G, Repic M, Landler L, Stránecký V, Dürnberger G, Keane T, Zuber J, Adams D, Flint J, Honzik T, Gut M, Beltran S, Mechtler K, Sherr E, Kmoch S, Gut I, Keays D. 2018. Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans. Nature Neuroscience. 21(2), 207–217.","chicago":"Gstrein, Thomas, Andrew Edwards, Anna Přistoupilová, Ines Leca, Martin Breuss, Sandra Pilat Carotta, Andi H Hansen, et al. “Mutations in Vps15 Perturb Neuronal Migration in Mice and Are Associated with Neurodevelopmental Disease in Humans.” Nature Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-017-0053-5.","short":"T. Gstrein, A. Edwards, A. Přistoupilová, I. Leca, M. Breuss, S. Pilat Carotta, A.H. Hansen, R. Tripathy, A. Traunbauer, T. Hochstoeger, G. Rosoklija, M. Repic, L. Landler, V. Stránecký, G. Dürnberger, T. Keane, J. Zuber, D. Adams, J. Flint, T. Honzik, M. Gut, S. Beltran, K. Mechtler, E. Sherr, S. Kmoch, I. Gut, D. Keays, Nature Neuroscience 21 (2018) 207–217.","ieee":"T. Gstrein et al., “Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans,” Nature Neuroscience, vol. 21, no. 2. Nature Publishing Group, pp. 207–217, 2018.","apa":"Gstrein, T., Edwards, A., Přistoupilová, A., Leca, I., Breuss, M., Pilat Carotta, S., … Keays, D. (2018). Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/s41593-017-0053-5","ama":"Gstrein T, Edwards A, Přistoupilová A, et al. Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans. Nature Neuroscience. 2018;21(2):207-217. doi:10.1038/s41593-017-0053-5","mla":"Gstrein, Thomas, et al. “Mutations in Vps15 Perturb Neuronal Migration in Mice and Are Associated with Neurodevelopmental Disease in Humans.” Nature Neuroscience, vol. 21, no. 2, Nature Publishing Group, 2018, pp. 207–17, doi:10.1038/s41593-017-0053-5."},"date_updated":"2023-09-13T08:59:52Z","extern":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","type":"journal_article","status":"public","_id":"547","page":"207 - 217","doi":"10.1038/s41593-017-0053-5","date_published":"2018-06-06T00:00:00Z","volume":21,"issue":"2","date_created":"2018-12-11T11:47:06Z","isi":1,"year":"2018","publication_status":"published","day":"06","language":[{"iso":"eng"}],"publication":"Nature Neuroscience","publisher":"Nature Publishing Group","month":"06","intvolume":" 21","abstract":[{"text":"The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling. The complete ablation of Vps15 results in the accumulation of autophagic substrates, the induction of apoptosis and severe cortical atrophy. Finally, we report that mutations in VPS15 are associated with cortical atrophy and epilepsy in humans. These data highlight the importance of the Vps15-Vps34 complex and the Nischarin-Pak1 signaling hub in the development of the telencephalon.","lang":"eng"}],"oa_version":"None","acknowledgement":"We also acknowledge the input of P. Potter and S. Wells from the mutagenesis program at MRC Harwell and the MRC funding that underpinned it (MC U142684172). We are indebted to R. Williams for modeling the VPS15 human mutation. We also thank the transgenic, bio-optics, proteomic and graphics services groups at the IMP/IMBA. We thank The National Center for Medical Genomics (LM2015091) for providing allelic frequencies in ethnically matched populations (project CZ.02.1.01/0.0/0.0/16_013/0001634). We thank Boehringer Ingelheim and the FWF for funding this research (D.A.K., I914, P24267). The human studies were funded by the European Community’s 7th Framework Program (FP7/2007-2013). S.K., A.P. and V.S. were supported by institutional programs of Charles University in Prague (UNCE 204011, PROGRES-Q26/LF1 and SVV 260367/2017). We acknowledge grants 15-28208A and RVO-VFN 64165 from the Ministry of Health of the Czech Republic and the project LQ1604 NPU II from the Ministry of Education."},{"extern":"1","ddc":["570","571"],"date_updated":"2023-09-20T11:37:25Z","file_date_updated":"2018-12-12T10:12:03Z","_id":"1107","status":"public","pubrep_id":"868","type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"file":[{"date_created":"2018-12-12T10:12:03Z","file_name":"IST-2017-868-v1+1_1-s2.0-S0166432816309160-main.pdf","date_updated":"2018-12-12T10:12:03Z","file_size":2291511,"creator":"system","file_id":"4921","content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["01664328"]},"publication_status":"published","volume":323,"oa_version":"Published Version","abstract":[{"text":"The generation, migration, and differentiation of neurons requires the functional integrity of the microtubule cytoskeleton. Mutations in the tubulin gene family are known to cause various neurological diseases including lissencephaly, ocular motor disorders, polymicrogyria and amyotrophic lateral sclerosis. We have previously reported that mutations in TUBB5 cause microcephaly that is accompanied by severe intellectual impairment and motor delay. Here we present the characterization of a Tubb5 mouse model that allows for the conditional expression of the pathogenic E401K mutation. Homozygous knockin animals exhibit a severe reduction in brain size and in body weight. These animals do not show any significant impairment in general activity, anxiety, or in the acoustic startle response, however, present with notable defects in motor coordination. When assessed on the static rod apparatus mice took longer to orient and often lost their balance completely. Interestingly, mutant animals also showed defects in prepulse inhibition, a phenotype associated with sensorimotor gating and considered an endophenotype for schizophrenia. This study provides insight into the behavioral consequences of tubulin gene mutations.","lang":"eng"}],"month":"04","intvolume":" 323","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Breuss, Martin, Andi H Hansen, Lukas Landler, and David Keays. “Brain Specific Knockin of the Pathogenic Tubb5 E401K Allele Causes Defects in Motor Coordination and Prepulse Inhibition.” Behavioural Brain Research. Elsevier, 2017. https://doi.org/10.1016/j.bbr.2017.01.029.","ista":"Breuss M, Hansen AH, Landler L, Keays D. 2017. Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition. Behavioural Brain Research. 323, 47–55.","mla":"Breuss, Martin, et al. “Brain Specific Knockin of the Pathogenic Tubb5 E401K Allele Causes Defects in Motor Coordination and Prepulse Inhibition.” Behavioural Brain Research, vol. 323, Elsevier, 2017, pp. 47–55, doi:10.1016/j.bbr.2017.01.029.","apa":"Breuss, M., Hansen, A. H., Landler, L., & Keays, D. (2017). Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition. Behavioural Brain Research. Elsevier. https://doi.org/10.1016/j.bbr.2017.01.029","ama":"Breuss M, Hansen AH, Landler L, Keays D. Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition. Behavioural Brain Research. 2017;323:47-55. doi:10.1016/j.bbr.2017.01.029","ieee":"M. Breuss, A. H. Hansen, L. Landler, and D. Keays, “Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition,” Behavioural Brain Research, vol. 323. Elsevier, pp. 47–55, 2017.","short":"M. Breuss, A.H. Hansen, L. Landler, D. Keays, Behavioural Brain Research 323 (2017) 47–55."},"title":"Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition","author":[{"first_name":"Martin","full_name":"Breuss, Martin","last_name":"Breuss"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","full_name":"Hansen, Andi H","last_name":"Hansen"},{"first_name":"Lukas","last_name":"Landler","full_name":"Landler, Lukas"},{"first_name":"David","last_name":"Keays","full_name":"Keays, David"}],"publist_id":"6262","external_id":{"isi":["000397369100007"]},"article_processing_charge":"No","day":"14","publication":"Behavioural Brain Research","has_accepted_license":"1","isi":1,"year":"2017","doi":"10.1016/j.bbr.2017.01.029","date_published":"2017-04-14T00:00:00Z","date_created":"2018-12-11T11:50:11Z","page":"47 - 55","acknowledgement":"Austrian Science Fund (FWF) for funding this research [I914,P21092]","quality_controlled":"1","publisher":"Elsevier","oa":1},{"page":"58 - 67","date_published":"2017-10-01T00:00:00Z","doi":"10.1016/j.mcn.2017.03.002","date_created":"2018-12-11T11:49:42Z","isi":1,"has_accepted_license":"1","year":"2017","day":"01","publication":"Molecular and Cellular Neuroscience","publisher":"Academic Press","quality_controlled":"1","oa":1,"publist_id":"6377","author":[{"full_name":"Breuss, Martin","last_name":"Breuss","first_name":"Martin"},{"first_name":"Ines","full_name":"Leca, Ines","last_name":"Leca"},{"first_name":"Thomas","last_name":"Gstrein","full_name":"Gstrein, Thomas"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","full_name":"Hansen, Andi H","last_name":"Hansen"},{"full_name":"Keays, David","last_name":"Keays","first_name":"David"}],"external_id":{"isi":["000415140700007"]},"article_processing_charge":"No","title":"Tubulins and brain development: The origins of functional specification","citation":{"chicago":"Breuss, Martin, Ines Leca, Thomas Gstrein, Andi H Hansen, and David Keays. “Tubulins and Brain Development: The Origins of Functional Specification.” Molecular and Cellular Neuroscience. Academic Press, 2017. https://doi.org/10.1016/j.mcn.2017.03.002.","ista":"Breuss M, Leca I, Gstrein T, Hansen AH, Keays D. 2017. Tubulins and brain development: The origins of functional specification. Molecular and Cellular Neuroscience. 84, 58–67.","mla":"Breuss, Martin, et al. “Tubulins and Brain Development: The Origins of Functional Specification.” Molecular and Cellular Neuroscience, vol. 84, Academic Press, 2017, pp. 58–67, doi:10.1016/j.mcn.2017.03.002.","ieee":"M. Breuss, I. Leca, T. Gstrein, A. H. Hansen, and D. Keays, “Tubulins and brain development: The origins of functional specification,” Molecular and Cellular Neuroscience, vol. 84. Academic Press, pp. 58–67, 2017.","short":"M. Breuss, I. Leca, T. Gstrein, A.H. Hansen, D. Keays, Molecular and Cellular Neuroscience 84 (2017) 58–67.","ama":"Breuss M, Leca I, Gstrein T, Hansen AH, Keays D. Tubulins and brain development: The origins of functional specification. Molecular and Cellular Neuroscience. 2017;84:58-67. doi:10.1016/j.mcn.2017.03.002","apa":"Breuss, M., Leca, I., Gstrein, T., Hansen, A. H., & Keays, D. (2017). Tubulins and brain development: The origins of functional specification. Molecular and Cellular Neuroscience. Academic Press. https://doi.org/10.1016/j.mcn.2017.03.002"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","volume":84,"publication_identifier":{"issn":["10447431"]},"publication_status":"published","file":[{"file_id":"4742","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"IST-2017-806-v1+2_1-s2.0-S1044743116302500-main_1_.pdf","date_created":"2018-12-12T10:09:19Z","creator":"system","file_size":1436377,"date_updated":"2018-12-12T10:09:19Z"}],"language":[{"iso":"eng"}],"scopus_import":"1","month":"10","intvolume":" 84","abstract":[{"lang":"eng","text":"The development of the vertebrate central nervous system is reliant on a complex cascade of biological processes that include mitotic division, relocation of migrating neurons, and the extension of dendritic and axonal processes. Each of these cellular events requires the diverse functional repertoire of the microtubule cytoskeleton for the generation of forces, assembly of macromolecular complexes and transport of molecules and organelles. The tubulins are a multi-gene family that encode for the constituents of microtubules, and have been implicated in a spectrum of neurological disorders. Evidence is building that different tubulins tune the functional properties of the microtubule cytoskeleton dependent on the cell type, developmental profile and subcellular localisation. Here we review of the origins of the functional specification of the tubulin gene family in the developing brain at a transcriptional, translational, and post-transcriptional level. We remind the reader that tubulins are not just loading controls for your average Western blot."}],"oa_version":"Published Version","department":[{"_id":"SiHi"}],"file_date_updated":"2018-12-12T10:09:19Z","date_updated":"2023-09-22T09:42:15Z","ddc":["571"],"type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"status":"public","pubrep_id":"806","_id":"1017"},{"title":"Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability","publist_id":"6379","author":[{"full_name":"Breuss, Martin","last_name":"Breuss","first_name":"Martin"},{"first_name":"Thai","full_name":"Nguyen, Thai","last_name":"Nguyen"},{"first_name":"Anjana","last_name":"Srivatsan","full_name":"Srivatsan, Anjana"},{"first_name":"Ines","last_name":"Leca","full_name":"Leca, Ines"},{"last_name":"Tian","full_name":"Tian, Guoling","first_name":"Guoling"},{"first_name":"Tanja","last_name":"Fritz","full_name":"Fritz, Tanja"},{"last_name":"Hansen","full_name":"Hansen, Andi H","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Musaev","full_name":"Musaev, Damir","first_name":"Damir"},{"last_name":"Mcevoy Venneri","full_name":"Mcevoy Venneri, Jennifer","first_name":"Jennifer"},{"last_name":"Kiely","full_name":"Kiely, James","first_name":"James"},{"full_name":"Rosti, Rasim","last_name":"Rosti","first_name":"Rasim"},{"last_name":"Scott","full_name":"Scott, Eric","first_name":"Eric"},{"first_name":"Uner","full_name":"Tan, Uner","last_name":"Tan"},{"first_name":"Richard","full_name":"Kolodner, Richard","last_name":"Kolodner"},{"first_name":"Nicholas","full_name":"Cowan, Nicholas","last_name":"Cowan"},{"first_name":"David","last_name":"Keays","full_name":"Keays, David"},{"last_name":"Gleeson","full_name":"Gleeson, Joseph","first_name":"Joseph"}],"external_id":{"isi":["000397066400002"]},"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ama":"Breuss M, Nguyen T, Srivatsan A, et al. Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability. Human Molecular Genetics. 2017;26(2):258-269. doi:10.1093/hmg/ddw383","apa":"Breuss, M., Nguyen, T., Srivatsan, A., Leca, I., Tian, G., Fritz, T., … Gleeson, J. (2017). Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability. Human Molecular Genetics. Oxford University Press. https://doi.org/10.1093/hmg/ddw383","ieee":"M. Breuss et al., “Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability,” Human Molecular Genetics, vol. 26, no. 2. Oxford University Press, pp. 258–269, 2017.","short":"M. Breuss, T. Nguyen, A. Srivatsan, I. Leca, G. Tian, T. Fritz, A.H. Hansen, D. Musaev, J. Mcevoy Venneri, J. Kiely, R. Rosti, E. Scott, U. Tan, R. Kolodner, N. Cowan, D. Keays, J. Gleeson, Human Molecular Genetics 26 (2017) 258–269.","mla":"Breuss, Martin, et al. “Uner Tan Syndrome Caused by a Homozygous TUBB2B Mutation Affecting Microtubule Stability.” Human Molecular Genetics, vol. 26, no. 2, Oxford University Press, 2017, pp. 258–69, doi:10.1093/hmg/ddw383.","ista":"Breuss M, Nguyen T, Srivatsan A, Leca I, Tian G, Fritz T, Hansen AH, Musaev D, Mcevoy Venneri J, Kiely J, Rosti R, Scott E, Tan U, Kolodner R, Cowan N, Keays D, Gleeson J. 2017. Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability. Human Molecular Genetics. 26(2), 258–269.","chicago":"Breuss, Martin, Thai Nguyen, Anjana Srivatsan, Ines Leca, Guoling Tian, Tanja Fritz, Andi H Hansen, et al. “Uner Tan Syndrome Caused by a Homozygous TUBB2B Mutation Affecting Microtubule Stability.” Human Molecular Genetics. Oxford University Press, 2017. https://doi.org/10.1093/hmg/ddw383."},"quality_controlled":"1","publisher":"Oxford University Press","date_published":"2017-01-01T00:00:00Z","doi":"10.1093/hmg/ddw383","date_created":"2018-12-11T11:49:42Z","page":"258 - 269","day":"01","publication":"Human Molecular Genetics","isi":1,"year":"2017","status":"public","type":"journal_article","_id":"1016","department":[{"_id":"SiHi"}],"date_updated":"2023-09-22T09:42:42Z","month":"01","intvolume":" 26","scopus_import":"1","oa_version":"None","abstract":[{"lang":"eng","text":"The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly referred to as the tubulinopathies. Here we report the addition of recessive quadrupedalism, also known as Uner Tan syndrome (UTS), to the growing list of diseases caused by tubulin variants. Analysis of a consanguineous UTS family identified a biallelic TUBB2B mutation, resulting in a p.R390Q amino acid substitution. In addition to the identifying quadrupedal locomotion, all three patients showed severe cerebellar hypoplasia. None, however, displayed the basal ganglia malformations typically associated with TUBB2B mutations. Functional analysis of the R390Q substitution revealed that it did not affect the ability of β-tubulin to fold or become assembled into the α/β-heterodimer, nor did it influence the incorporation of mutant-containing heterodimers into microtubule polymers. The 390Q mutation in S. cerevisiae TUB2 did not affect growth under basal conditions, but did result in increased sensitivity to microtubule-depolymerizing drugs, indicative of a mild impact of this mutation on microtubule function. The TUBB2B mutation described here represents an unusual recessive mode of inheritance for missense-mediated tubulinopathies and reinforces the sensitivity of the developing cerebellum to microtubule defects."}],"issue":"2","volume":26,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["09646906"]},"publication_status":"published"},{"date_created":"2018-12-11T11:49:25Z","date_published":"2017-06-28T00:00:00Z","doi":"10.3389/fncel.2017.00176","publication":"Frontiers in Cellular Neuroscience","day":"28","year":"2017","has_accepted_license":"1","isi":1,"oa":1,"quality_controlled":"1","publisher":"Frontiers Research Foundation","title":"Cell polarity in cerebral cortex development - cellular architecture shaped by biochemical networks","external_id":{"isi":["000404486700001"]},"article_processing_charge":"Yes","author":[{"last_name":"Hansen","full_name":"Hansen, Andi H","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Düllberg","full_name":"Düllberg, Christian F","orcid":"0000-0001-6335-9748","first_name":"Christian F","id":"459064DC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christine","id":"34CAE85C-F248-11E8-B48F-1D18A9856A87","last_name":"Mieck","full_name":"Mieck, Christine","orcid":"0000-0003-1919-7416"},{"id":"462D4284-F248-11E8-B48F-1D18A9856A87","first_name":"Martin","last_name":"Loose","full_name":"Loose, Martin","orcid":"0000-0001-7309-9724"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"publist_id":"6445","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Hansen, Andi H., et al. “Cell Polarity in Cerebral Cortex Development - Cellular Architecture Shaped by Biochemical Networks.” Frontiers in Cellular Neuroscience, vol. 11, 176, Frontiers Research Foundation, 2017, doi:10.3389/fncel.2017.00176.","ama":"Hansen AH, Düllberg CF, Mieck C, Loose M, Hippenmeyer S. Cell polarity in cerebral cortex development - cellular architecture shaped by biochemical networks. Frontiers in Cellular Neuroscience. 2017;11. doi:10.3389/fncel.2017.00176","apa":"Hansen, A. H., Düllberg, C. F., Mieck, C., Loose, M., & Hippenmeyer, S. (2017). Cell polarity in cerebral cortex development - cellular architecture shaped by biochemical networks. Frontiers in Cellular Neuroscience. Frontiers Research Foundation. https://doi.org/10.3389/fncel.2017.00176","short":"A.H. Hansen, C.F. Düllberg, C. Mieck, M. Loose, S. Hippenmeyer, Frontiers in Cellular Neuroscience 11 (2017).","ieee":"A. H. Hansen, C. F. Düllberg, C. Mieck, M. Loose, and S. Hippenmeyer, “Cell polarity in cerebral cortex development - cellular architecture shaped by biochemical networks,” Frontiers in Cellular Neuroscience, vol. 11. Frontiers Research Foundation, 2017.","chicago":"Hansen, Andi H, Christian F Düllberg, Christine Mieck, Martin Loose, and Simon Hippenmeyer. “Cell Polarity in Cerebral Cortex Development - Cellular Architecture Shaped by Biochemical Networks.” Frontiers in Cellular Neuroscience. Frontiers Research Foundation, 2017. https://doi.org/10.3389/fncel.2017.00176.","ista":"Hansen AH, Düllberg CF, Mieck C, Loose M, Hippenmeyer S. 2017. Cell polarity in cerebral cortex development - cellular architecture shaped by biochemical networks. Frontiers in Cellular Neuroscience. 11, 176."},"project":[{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-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"},{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"25985A36-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"T00817-B21","name":"The biochemical basis of PAR polarization"}],"article_number":"176","ec_funded":1,"related_material":{"record":[{"relation":"dissertation_contains","id":"9962","status":"public"}]},"volume":11,"language":[{"iso":"eng"}],"file":[{"file_name":"IST-2017-830-v1+1_2017_Hansen_CellPolarity.pdf","date_created":"2018-12-12T10:09:40Z","file_size":2153858,"date_updated":"2020-07-14T12:48:16Z","creator":"system","file_id":"4764","checksum":"dc1f5a475b918d09a0f9f587400b1626","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"publication_status":"published","publication_identifier":{"issn":["16625102"]},"intvolume":" 11","month":"06","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers. The establishment of specific morphological and physiological features in individual neurons needs to be regulated with high precision. Impairments in the sequential developmental programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture which is thought to represent the major underlying cause for several neurological disorders including neurodevelopmental and psychiatric diseases. In this review we discuss the role of cell polarity at sequential stages during cortex development. We first provide an overview of morphological cell polarity features in cortical neural stem cells and newly-born postmitotic neurons. We then synthesize a conceptual molecular and biochemical framework how cell polarity is established at the cellular level through a break in symmetry in nascent cortical projection neurons. Lastly we provide a perspective how the molecular mechanisms applying to single cells could be probed and integrated in an in vivo and tissue-wide context."}],"department":[{"_id":"SiHi"},{"_id":"MaLo"}],"file_date_updated":"2020-07-14T12:48:16Z","ddc":["570"],"date_updated":"2024-03-27T23:30:40Z","pubrep_id":"830","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"960"},{"_id":"1106","status":"public","type":"journal_article","extern":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Isrie M, Breuss M, Tian G, Hansen AH, Cristofoli F, Morandell J, Kupchinsky ZA, Sifrim A, Rodriguez Rodriguez C, Dapena EP, Doonanco K, Leonard N, Tinsa F, Moortgat S, Ulucan H, Koparir E, Karaca E, Katsanis N, Marton V, Vermeesch JR, Davis EE, Cowan NJ, Keays D, Van Esch H. 2015. Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type. The American Journal of Human Genetics. 97(6), 790–800.","chicago":"Isrie, Mala, Martin Breuss, Guoling Tian, Andi H Hansen, Francesca Cristofoli, Jasmin Morandell, Zachari A Kupchinsky, et al. “Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.” The American Journal of Human Genetics. Cell Press, 2015. https://doi.org/10.1016/j.ajhg.2015.10.014.","apa":"Isrie, M., Breuss, M., Tian, G., Hansen, A. H., Cristofoli, F., Morandell, J., … Van Esch, H. (2015). Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type. The American Journal of Human Genetics. Cell Press. https://doi.org/10.1016/j.ajhg.2015.10.014","ama":"Isrie M, Breuss M, Tian G, et al. Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type. The American Journal of Human Genetics. 2015;97(6):790-800. doi:10.1016/j.ajhg.2015.10.014","short":"M. Isrie, M. Breuss, G. Tian, A.H. Hansen, F. Cristofoli, J. Morandell, Z.A. Kupchinsky, A. Sifrim, C. Rodriguez Rodriguez, E.P. Dapena, K. Doonanco, N. Leonard, F. Tinsa, S. Moortgat, H. Ulucan, E. Koparir, E. Karaca, N. Katsanis, V. Marton, J.R. Vermeesch, E.E. Davis, N.J. Cowan, D. Keays, H. Van Esch, The American Journal of Human Genetics 97 (2015) 790–800.","ieee":"M. Isrie et al., “Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type,” The American Journal of Human Genetics, vol. 97, no. 6. Cell Press, pp. 790–800, 2015.","mla":"Isrie, Mala, et al. “Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.” The American Journal of Human Genetics, vol. 97, no. 6, Cell Press, 2015, pp. 790–800, doi:10.1016/j.ajhg.2015.10.014."},"date_updated":"2021-01-12T06:48:19Z","title":"Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type","author":[{"full_name":"Isrie, Mala","last_name":"Isrie","first_name":"Mala"},{"full_name":"Breuss, Martin","last_name":"Breuss","first_name":"Martin"},{"full_name":"Tian, Guoling","last_name":"Tian","first_name":"Guoling"},{"first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","full_name":"Hansen, Andi H"},{"last_name":"Cristofoli","full_name":"Cristofoli, Francesca","first_name":"Francesca"},{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"last_name":"Kupchinsky","full_name":"Kupchinsky, Zachari A","first_name":"Zachari A"},{"last_name":"Sifrim","full_name":"Sifrim, Alejandro","first_name":"Alejandro"},{"first_name":"Celia","last_name":"Rodriguez Rodriguez","full_name":"Rodriguez Rodriguez, Celia"},{"first_name":"Elena P","full_name":"Dapena, Elena P","last_name":"Dapena"},{"last_name":"Doonanco","full_name":"Doonanco, Kurston","first_name":"Kurston"},{"first_name":"Norma","full_name":"Leonard, Norma","last_name":"Leonard"},{"first_name":"Faten","full_name":"Tinsa, Faten","last_name":"Tinsa"},{"first_name":"Stéphanie","last_name":"Moortgat","full_name":"Moortgat, Stéphanie"},{"last_name":"Ulucan","full_name":"Ulucan, Hakan","first_name":"Hakan"},{"first_name":"Erkan","full_name":"Koparir, Erkan","last_name":"Koparir"},{"full_name":"Karaca, Ender","last_name":"Karaca","first_name":"Ender"},{"first_name":"Nicholas","last_name":"Katsanis","full_name":"Katsanis, Nicholas"},{"full_name":"Marton, Valeria","last_name":"Marton","first_name":"Valeria"},{"last_name":"Vermeesch","full_name":"Vermeesch, Joris R","first_name":"Joris R"},{"full_name":"Davis, Erica E","last_name":"Davis","first_name":"Erica E"},{"first_name":"Nicholas J","full_name":"Cowan, Nicholas J","last_name":"Cowan"},{"first_name":"David","full_name":"Keays, David","last_name":"Keays"},{"first_name":"Hilde","last_name":"Van Esch","full_name":"Van Esch, Hilde"}],"publist_id":"6264","oa_version":"None","abstract":[{"text":"Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a β-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect.","lang":"eng"}],"month":"12","intvolume":" 97","quality_controlled":"1","publisher":"Cell Press","day":"03","language":[{"iso":"eng"}],"publication":"The American Journal of Human Genetics","year":"2015","publication_status":"published","date_published":"2015-12-03T00:00:00Z","issue":"6","doi":"10.1016/j.ajhg.2015.10.014","volume":97,"date_created":"2018-12-11T11:50:11Z","page":"790 - 800"}]