[{"date_updated":"2021-01-12T08:15:42Z","ddc":["570"],"file_date_updated":"2020-07-14T12:48:03Z","department":[{"_id":"SiHi"}],"_id":"7814","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)"},"article_type":"original","type":"journal_article","status":"public","publication_status":"published","publication_identifier":{"issn":["2504-284X"]},"language":[{"iso":"eng"}],"file":[{"file_size":1402146,"date_updated":"2020-07-14T12:48:03Z","creator":"dernst","file_name":"2020_FrontiersEduc_Beattie.pdf","date_created":"2020-05-11T11:34:08Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","checksum":"a24ec24e38d843341ae620ec76c53688","file_id":"7818"}],"ec_funded":1,"volume":5,"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."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"oa_version":"Published Version","intvolume":" 5","month":"05","citation":{"ista":"Beattie RJ, Hippenmeyer S, Pauler F. 2020. SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. 5, 48.","chicago":"Beattie, Robert J, Simon Hippenmeyer, and Florian Pauler. “SCOPES: Sparking Curiosity through Open-Source Platforms in Education and Science.” Frontiers in Education. Frontiers Media, 2020. https://doi.org/10.3389/feduc.2020.00048.","ama":"Beattie RJ, Hippenmeyer S, Pauler F. SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. 2020;5. doi:10.3389/feduc.2020.00048","apa":"Beattie, R. J., Hippenmeyer, S., & Pauler, F. (2020). SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. Frontiers Media. https://doi.org/10.3389/feduc.2020.00048","ieee":"R. J. Beattie, S. Hippenmeyer, and F. Pauler, “SCOPES: Sparking curiosity through Open-Source platforms in education and science,” Frontiers in Education, vol. 5. Frontiers Media, 2020.","short":"R.J. Beattie, S. Hippenmeyer, F. Pauler, Frontiers in Education 5 (2020).","mla":"Beattie, Robert J., et al. “SCOPES: Sparking Curiosity through Open-Source Platforms in Education and Science.” Frontiers in Education, vol. 5, 48, Frontiers Media, 2020, doi:10.3389/feduc.2020.00048."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","author":[{"id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","last_name":"Beattie","orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","full_name":"Pauler, Florian","last_name":"Pauler"}],"title":"SCOPES: Sparking curiosity through Open-Source platforms in education and science","article_number":"48","project":[{"_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","grant_number":"M02416"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"year":"2020","has_accepted_license":"1","publication":"Frontiers in Education","day":"08","date_created":"2020-05-11T08:18:48Z","date_published":"2020-05-08T00:00:00Z","doi":"10.3389/feduc.2020.00048","oa":1,"publisher":"Frontiers Media","quality_controlled":"1"},{"file":[{"file_id":"7261","checksum":"ebf1ed522f4e0be8d94c939c1806a709","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2020_NatureComm_Laukoter.pdf","date_created":"2020-01-13T07:42:31Z","creator":"dernst","file_size":8063333,"date_updated":"2020-07-14T12:47:54Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2041-1723"]},"publication_status":"published","volume":11,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/","relation":"press_release","description":"News on IST Homepage"}]},"ec_funded":1,"oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor cell and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype."}],"month":"01","intvolume":" 11","scopus_import":"1","ddc":["570"],"date_updated":"2023-08-17T14:23:41Z","file_date_updated":"2020-07-14T12:47:54Z","department":[{"_id":"SiHi"}],"_id":"7253","status":"public","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)"},"day":"10","publication":"Nature Communications","has_accepted_license":"1","isi":1,"year":"2020","date_published":"2020-01-10T00:00:00Z","doi":"10.1038/s41467-019-14077-2","date_created":"2020-01-11T10:42:48Z","quality_controlled":"1","publisher":"Springer Nature","oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications, vol. 11, 195, Springer Nature, 2020, doi:10.1038/s41467-019-14077-2.","ieee":"S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer, “Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development,” Nature Communications, vol. 11. Springer Nature, 2020.","short":"S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer, Nature Communications 11 (2020).","ama":"Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 2020;11. doi:10.1038/s41467-019-14077-2","apa":"Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., & Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-14077-2","chicago":"Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-019-14077-2.","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."},"title":"Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development","author":[{"first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","last_name":"Laukoter"},{"orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J","last_name":"Beattie","first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg"},{"first_name":"Keiichi I.","full_name":"Nakayama, Keiichi I.","last_name":"Nakayama"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"article_processing_charge":"No","external_id":{"isi":["000551459000005"]},"article_number":"195","project":[{"grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"}]},{"has_accepted_license":"1","isi":1,"year":"2020","day":"23","publication":"Neuron","page":"1160-1179.e9","doi":"10.1016/j.neuron.2020.06.031","date_published":"2020-09-23T00:00:00Z","date_created":"2020-07-23T16:03:12Z","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.","quality_controlled":"1","publisher":"Elsevier","oa":1,"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","author":[{"first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","last_name":"Laukoter"},{"full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian"},{"orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J","last_name":"Beattie","first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen","full_name":"Hansen, Andi H"},{"first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher"},{"last_name":"Penz","full_name":"Penz, Thomas","first_name":"Thomas"},{"full_name":"Bock, Christoph","orcid":"0000-0001-6091-3088","last_name":"Bock","first_name":"Christoph"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","external_id":{"isi":["000579698700006"]},"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"},{"_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression"},{"grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425"},{"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"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"publication_identifier":{"issn":["0896-6273"]},"publication_status":"published","file":[{"file_size":8911830,"date_updated":"2020-12-02T09:26:46Z","creator":"dernst","file_name":"2020_Neuron_Laukoter.pdf","date_created":"2020-12-02T09:26:46Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"file_id":"8828","checksum":"7becdc16a6317304304631087ae7dd7f"}],"language":[{"iso":"eng"}],"issue":"6","volume":107,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/","relation":"press_release","description":"News on IST Website"}]},"ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"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."}],"oa_version":"Published Version","scopus_import":"1","month":"09","intvolume":" 107","date_updated":"2023-08-22T08:20:11Z","ddc":["570"],"file_date_updated":"2020-12-02T09:26:46Z","department":[{"_id":"SiHi"}],"_id":"8162","type":"journal_article","article_type":"original","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"},{"intvolume":" 9","month":"12","abstract":[{"text":"Development of the nervous system undergoes important transitions, including one from neurogenesis to gliogenesis which occurs late during embryonic gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic Analysis with Double Markers (MADM) with quantitative and computational methods. Results reveal that developmental gliogenesis in the cerebral cortex occurs in a fraction of earlier neurogenic clones, accelerating around E16.5, and giving rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices. A broad range in the proliferation capacity, symmetry of clones, and competitive advantage of MADM cells was evident in clones that contained one cellular lineage with double dosage of Egfr relative to their environment, while their sibling Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia in MADM clones balance out regardless of significant alterations in clonal symmetries. The variability in glial clones shows stochastic patterns that we define mathematically, which are different from the deterministic patterns in neuronal clones. This study sets a foundation for studying the biological significance of stochastic and deterministic clonal principles underlying tissue development, and identifying mechanisms that differentiate between neurogenesis and gliogenesis.","lang":"eng"}],"oa_version":"Published Version","ec_funded":1,"issue":"12","volume":9,"publication_status":"published","publication_identifier":{"issn":["2073-4409"]},"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"8950","checksum":"5095cbdc728c9a510c5761cf60a8861c","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2020_Cells_Zhang.pdf","date_created":"2020-12-14T08:09:43Z","file_size":3504525,"date_updated":"2020-12-14T08:09:43Z","creator":"dernst"}],"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)"},"article_type":"original","type":"journal_article","status":"public","_id":"8949","file_date_updated":"2020-12-14T08:09:43Z","department":[{"_id":"SiHi"}],"date_updated":"2023-08-24T10:57:48Z","ddc":["570"],"oa":1,"quality_controlled":"1","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.","date_created":"2020-12-14T08:04:03Z","date_published":"2020-12-11T00:00:00Z","doi":"10.3390/cells9122662","year":"2020","isi":1,"has_accepted_license":"1","publication":"Cells","day":"11","project":[{"grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"article_number":"2662","article_processing_charge":"No","external_id":{"isi":["000601787300001"]},"author":[{"last_name":"Zhang","full_name":"Zhang, Xuying","first_name":"Xuying"},{"last_name":"Mennicke","full_name":"Mennicke, Christine V.","first_name":"Christine V."},{"first_name":"Guanxi","full_name":"Xiao, Guanxi","last_name":"Xiao"},{"id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","last_name":"Beattie","orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J"},{"last_name":"Haider","full_name":"Haider, Mansoor","first_name":"Mansoor"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Ghashghaei, H. Troy","last_name":"Ghashghaei","first_name":"H. Troy"}],"title":"Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage","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 et al., “Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage,” Cells, vol. 9, no. 12. MDPI, 2020.","ama":"Zhang X, Mennicke CV, Xiao G, et al. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. 2020;9(12). doi:10.3390/cells9122662","apa":"Zhang, X., Mennicke, C. V., Xiao, G., Beattie, R. J., Haider, M., Hippenmeyer, S., & Ghashghaei, H. T. (2020). Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. MDPI. https://doi.org/10.3390/cells9122662","mla":"Zhang, Xuying, et al. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” Cells, vol. 9, no. 12, 2662, MDPI, 2020, doi:10.3390/cells9122662.","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.","chicago":"Zhang, Xuying, Christine V. Mennicke, Guanxi Xiao, Robert J Beattie, Mansoor Haider, Simon Hippenmeyer, and H. Troy Ghashghaei. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” Cells. MDPI, 2020. https://doi.org/10.3390/cells9122662."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"publication_identifier":{"issn":["1940-087X"]},"publication_status":"published","file":[{"checksum":"3154ea7f90b9fb45e084cd1c2770597d","file_id":"7816","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf","date_created":"2020-05-11T08:28:38Z","creator":"rbeattie","file_size":1352186,"date_updated":"2020-07-14T12:48:03Z"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"status":"public","id":"7902","relation":"part_of_dissertation"}]},"issue":"159","ec_funded":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."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"oa_version":"Published Version","scopus_import":"1","month":"05","date_updated":"2024-03-27T23:30:41Z","ddc":["570"],"file_date_updated":"2020-07-14T12:48:03Z","department":[{"_id":"SiHi"}],"_id":"7815","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","has_accepted_license":"1","isi":1,"year":"2020","day":"08","publication":"Journal of Visual Experiments","doi":"10.3791/61147","date_published":"2020-05-08T00:00:00Z","date_created":"2020-05-11T08:31:20Z","publisher":"MyJove Corporation","quality_controlled":"1","oa":1,"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.","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.","ama":"Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. 2020;(159). doi:10.3791/61147","apa":"Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen, A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147","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":"Beattie, Robert J","orcid":"0000-0002-8483-8753","last_name":"Beattie","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"},{"last_name":"Amberg","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Cheung","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T"},{"full_name":"Contreras, Ximena","last_name":"Contreras","first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hansen","full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"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)","article_number":"e61147","project":[{"call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","grant_number":"M02416"},{"grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812"},{"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":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Llorca, Alfredo, et al. “A Stochastic Framework of Neurogenesis Underlies the Assembly of Neocortical Cytoarchitecture.” ELife, vol. 8, e51381, eLife Sciences Publications, 2019, doi:10.7554/eLife.51381.","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. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.51381","ama":"Llorca A, Ciceri G, Beattie RJ, et al. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. eLife. 2019;8. doi:10.7554/eLife.51381","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).","ieee":"A. Llorca et al., “A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture,” eLife, vol. 8. eLife Sciences Publications, 2019.","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.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.51381.","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."},"title":"A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture","article_processing_charge":"No","external_id":{"isi":["000508156800001"],"pmid":["31736464"]},"author":[{"last_name":"Llorca","full_name":"Llorca, Alfredo","first_name":"Alfredo"},{"first_name":"Gabriele","full_name":"Ciceri, Gabriele","last_name":"Ciceri"},{"id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J","last_name":"Beattie"},{"full_name":"Wong, Fong Kuan","last_name":"Wong","first_name":"Fong Kuan"},{"full_name":"Diana, Giovanni","last_name":"Diana","first_name":"Giovanni"},{"first_name":"Eleni","full_name":"Serafeimidou-Pouliou, Eleni","last_name":"Serafeimidou-Pouliou"},{"last_name":"Fernández-Otero","full_name":"Fernández-Otero, Marian","first_name":"Marian"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen","full_name":"Streicher, Carmen","last_name":"Streicher"},{"last_name":"Arnold","full_name":"Arnold, Sebastian J.","first_name":"Sebastian J."},{"first_name":"Martin","last_name":"Meyer","full_name":"Meyer, Martin"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"},{"last_name":"Maravall","full_name":"Maravall, Miguel","first_name":"Miguel"},{"last_name":"Marín","full_name":"Marín, Oscar","first_name":"Oscar"}],"article_number":"e51381","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"},{"name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","grant_number":"M02416","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425"}],"publication":"eLife","day":"18","year":"2019","has_accepted_license":"1","isi":1,"date_created":"2019-12-22T23:00:42Z","doi":"10.7554/eLife.51381","date_published":"2019-11-18T00:00:00Z","oa":1,"quality_controlled":"1","publisher":"eLife Sciences Publications","ddc":["570"],"date_updated":"2023-09-06T14:38:39Z","department":[{"_id":"SiHi"}],"file_date_updated":"2020-07-14T12:47:53Z","_id":"7202","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","article_type":"original","language":[{"iso":"eng"}],"file":[{"checksum":"b460ecc33e1a68265e7adea775021f3a","file_id":"7503","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2019_eLife_Llorca.pdf","date_created":"2020-02-18T15:19:26Z","file_size":2960543,"date_updated":"2020-07-14T12:47:53Z","creator":"dernst"}],"publication_status":"published","publication_identifier":{"eissn":["2050084X"]},"ec_funded":1,"volume":8,"pmid":1,"oa_version":"Published Version","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"}],"intvolume":" 8","month":"11","scopus_import":"1"},{"_id":"8547","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"},{"grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425"}],"status":"public","type":"preprint","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T08:20:00Z","citation":{"ieee":"A. Llorca et al., “Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture,” bioRxiv. Cold Spring Harbor Laboratory.","short":"A. Llorca, G. Ciceri, R.J. Beattie, F.K. Wong, G. Diana, E. Serafeimidou, M. Fernández-Otero, C. Streicher, S.J. Arnold, M. Meyer, S. Hippenmeyer, M. Maravall, O. Marín, BioRxiv (n.d.).","apa":"Llorca, A., Ciceri, G., Beattie, R. J., Wong, F. K., Diana, G., Serafeimidou, E., … Marín, O. (n.d.). Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/494088","ama":"Llorca A, Ciceri G, Beattie RJ, et al. Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture. bioRxiv. doi:10.1101/494088","mla":"Llorca, Alfredo, et al. “Heterogeneous Progenitor Cell Behaviors Underlie the Assembly of Neocortical Cytoarchitecture.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/494088.","ista":"Llorca A, Ciceri G, Beattie RJ, Wong FK, Diana G, Serafeimidou E, Fernández-Otero M, Streicher C, Arnold SJ, Meyer M, Hippenmeyer S, Maravall M, Marín O. Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture. bioRxiv, 10.1101/494088.","chicago":"Llorca, Alfredo, Gabriele Ciceri, Robert J Beattie, Fong K. Wong, Giovanni Diana, Eleni Serafeimidou, Marian Fernández-Otero, et al. “Heterogeneous Progenitor Cell Behaviors Underlie the Assembly of Neocortical Cytoarchitecture.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/494088."},"title":"Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture","department":[{"_id":"SiHi"}],"article_processing_charge":"No","author":[{"first_name":"Alfredo","last_name":"Llorca","full_name":"Llorca, Alfredo"},{"last_name":"Ciceri","full_name":"Ciceri, Gabriele","first_name":"Gabriele"},{"full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","last_name":"Beattie","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J"},{"full_name":"Wong, Fong K.","last_name":"Wong","first_name":"Fong K."},{"first_name":"Giovanni","full_name":"Diana, Giovanni","last_name":"Diana"},{"first_name":"Eleni","full_name":"Serafeimidou, Eleni","last_name":"Serafeimidou"},{"full_name":"Fernández-Otero, Marian","last_name":"Fernández-Otero","first_name":"Marian"},{"full_name":"Streicher, Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"full_name":"Arnold, Sebastian J.","last_name":"Arnold","first_name":"Sebastian J."},{"last_name":"Meyer","full_name":"Meyer, Martin","first_name":"Martin"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Maravall","full_name":"Maravall, Miguel","first_name":"Miguel"},{"first_name":"Oscar","full_name":"Marín, Oscar","last_name":"Marín"}],"acknowledgement":"We thank I. Andrew and S.E. Bae for excellent technical assistance, F. Gage for plasmids, and K. Nave (Nex-Cre) for mouse colonies. We thank members of the Marín and Rico laboratories for stimulating discussions and ideas. Our research on this topic is supported by grants from the European Research Council (ERC-2017-AdG 787355 to O.M and ERC2016-CoG 725780 to S.H.) and Wellcome Trust (103714MA) to O.M. L.L. was the recipient of an EMBO long-term postdoctoral fellowship, R.B. received support from FWF Lise-Meitner program (M 2416) and F.K.W. was supported by an EMBO postdoctoral fellowship and is currently a Marie Skłodowska-Curie Fellow from the European Commission under the H2020 Programme.","oa_version":"Preprint","abstract":[{"text":"The cerebral cortex contains multiple hierarchically organized areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have quantitatively investigated the neuronal output of individual progenitor cells in the ventricular zone of the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. We found that individual cortical progenitor cells show a high degree of stochasticity and generate pyramidal cell lineages that adopt a wide range of laminar configurations. Mathematical modelling these lineage data suggests that a small number of progenitor cell populations, each generating pyramidal cells following different stochastic developmental programs, suffice to generate the heterogenous complement of pyramidal cell lineages that collectively build the complex cytoarchitecture of the neocortex.","lang":"eng"}],"month":"12","main_file_link":[{"url":"https://doi.org/10.1101/494088","open_access":"1"}],"oa":1,"publisher":"Cold Spring Harbor Laboratory","language":[{"iso":"eng"}],"publication":"bioRxiv","day":"13","publication_status":"submitted","year":"2018","date_created":"2020-09-21T12:01:50Z","ec_funded":1,"date_published":"2018-12-13T00:00:00Z","doi":"10.1101/494088"},{"project":[{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"grant_number":"RGP0053/2014","name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","_id":"25D7962E-B435-11E9-9278-68D0E5697425"}],"author":[{"last_name":"Beattie","orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J"},{"first_name":"Maria P","id":"2C67902A-F248-11E8-B48F-1D18A9856A87","full_name":"Postiglione, Maria P","last_name":"Postiglione"},{"last_name":"Burnett","full_name":"Burnett, Laura","orcid":"0000-0002-8937-410X","id":"3B717F68-F248-11E8-B48F-1D18A9856A87","first_name":"Laura"},{"id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne","last_name":"Laukoter","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne"},{"first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","full_name":"Streicher, Carmen"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler"},{"first_name":"Guanxi","last_name":"Xiao","full_name":"Xiao, Guanxi"},{"first_name":"Olga","last_name":"Klezovitch","full_name":"Klezovitch, Olga"},{"first_name":"Valeri","last_name":"Vasioukhin","full_name":"Vasioukhin, Valeri"},{"first_name":"Troy","full_name":"Ghashghaei, Troy","last_name":"Ghashghaei"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer"}],"publist_id":"6473","article_processing_charge":"No","external_id":{"isi":["000400466700011"]},"title":"Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells","citation":{"ista":"Beattie RJ, Postiglione MP, Burnett L, Laukoter S, Streicher C, Pauler F, Xiao G, Klezovitch O, Vasioukhin V, Ghashghaei T, Hippenmeyer S. 2017. Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. Neuron. 94(3), 517–533.e3.","chicago":"Beattie, Robert J, Maria P Postiglione, Laura Burnett, Susanne Laukoter, Carmen Streicher, Florian Pauler, Guanxi Xiao, et al. “Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” Neuron. Cell Press, 2017. https://doi.org/10.1016/j.neuron.2017.04.012.","ama":"Beattie RJ, Postiglione MP, Burnett L, et al. Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. Neuron. 2017;94(3):517-533.e3. doi:10.1016/j.neuron.2017.04.012","apa":"Beattie, R. J., Postiglione, M. P., Burnett, L., Laukoter, S., Streicher, C., Pauler, F., … Hippenmeyer, S. (2017). Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. Neuron. Cell Press. https://doi.org/10.1016/j.neuron.2017.04.012","ieee":"R. J. Beattie et al., “Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells,” Neuron, vol. 94, no. 3. Cell Press, p. 517–533.e3, 2017.","short":"R.J. Beattie, M.P. Postiglione, L. Burnett, S. Laukoter, C. Streicher, F. Pauler, G. Xiao, O. Klezovitch, V. Vasioukhin, T. Ghashghaei, S. Hippenmeyer, Neuron 94 (2017) 517–533.e3.","mla":"Beattie, Robert J., et al. “Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” Neuron, vol. 94, no. 3, Cell Press, 2017, p. 517–533.e3, doi:10.1016/j.neuron.2017.04.012."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Cell Press","quality_controlled":"1","page":"517 - 533.e3","date_published":"2017-05-03T00:00:00Z","doi":"10.1016/j.neuron.2017.04.012","date_created":"2018-12-11T11:49:20Z","isi":1,"year":"2017","day":"03","publication":"Neuron","type":"journal_article","status":"public","_id":"944","department":[{"_id":"SiHi"},{"_id":"MaJö"}],"date_updated":"2023-09-26T15:37:02Z","scopus_import":"1","month":"05","intvolume":" 94","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms."}],"oa_version":"None","issue":"3","volume":94,"ec_funded":1,"publication_identifier":{"issn":["08966273"]},"publication_status":"published","language":[{"iso":"eng"}]},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_updated":"2023-09-26T16:20:09Z","citation":{"mla":"Pfurr, Sabrina, et al. “The E2A Splice Variant E47 Regulates the Differentiation of Projection Neurons via P57(KIP2) during Cortical Development.” Development, vol. 144, Company of Biologists, 2017, pp. 3917–31, doi:10.1242/dev.145698.","ieee":"S. Pfurr et al., “The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development,” Development, vol. 144. Company of Biologists, pp. 3917–3931, 2017.","short":"S. Pfurr, Y. Chu, C. Bohrer, F. Greulich, R.J. Beattie, K. Mammadzada, M. Hils, S. Arnold, V. Taylor, K. Schachtrup, N.H. Uhlenhaut, C. Schachtrup, Development 144 (2017) 3917–3931.","ama":"Pfurr S, Chu Y, Bohrer C, et al. The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development. Development. 2017;144:3917-3931. doi:10.1242/dev.145698","apa":"Pfurr, S., Chu, Y., Bohrer, C., Greulich, F., Beattie, R. J., Mammadzada, K., … Schachtrup, C. (2017). The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development. Development. Company of Biologists. https://doi.org/10.1242/dev.145698","chicago":"Pfurr, Sabrina, Yu Chu, Christian Bohrer, Franziska Greulich, Robert J Beattie, Könül Mammadzada, Miriam Hils, et al. “The E2A Splice Variant E47 Regulates the Differentiation of Projection Neurons via P57(KIP2) during Cortical Development.” Development. Company of Biologists, 2017. https://doi.org/10.1242/dev.145698.","ista":"Pfurr S, Chu Y, Bohrer C, Greulich F, Beattie RJ, Mammadzada K, Hils M, Arnold S, Taylor V, Schachtrup K, Uhlenhaut NH, Schachtrup C. 2017. The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development. Development. 144, 3917–3931."},"department":[{"_id":"SiHi"}],"title":"The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development","author":[{"full_name":"Pfurr, Sabrina","last_name":"Pfurr","first_name":"Sabrina"},{"last_name":"Chu","full_name":"Chu, Yu","first_name":"Yu"},{"first_name":"Christian","full_name":"Bohrer, Christian","last_name":"Bohrer"},{"first_name":"Franziska","full_name":"Greulich, Franziska","last_name":"Greulich"},{"full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","last_name":"Beattie","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J"},{"full_name":"Mammadzada, Könül","last_name":"Mammadzada","first_name":"Könül"},{"first_name":"Miriam","full_name":"Hils, Miriam","last_name":"Hils"},{"full_name":"Arnold, Sebastian","last_name":"Arnold","first_name":"Sebastian"},{"full_name":"Taylor, Verdon","last_name":"Taylor","first_name":"Verdon"},{"full_name":"Schachtrup, Kristina","last_name":"Schachtrup","first_name":"Kristina"},{"first_name":"N Henriette","full_name":"Uhlenhaut, N Henriette","last_name":"Uhlenhaut"},{"first_name":"Christian","full_name":"Schachtrup, Christian","last_name":"Schachtrup"}],"publist_id":"6846","article_processing_charge":"No","external_id":{"isi":["000414025600007"]},"_id":"805","status":"public","type":"journal_article","day":"31","publication":"Development","language":[{"iso":"eng"}],"isi":1,"publication_status":"published","year":"2017","volume":144,"date_published":"2017-10-31T00:00:00Z","doi":"10.1242/dev.145698","date_created":"2018-12-11T11:48:36Z","page":"3917 - 3931","oa_version":"None","abstract":[{"lang":"eng","text":"During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14.5, while depletion of the alternatively spliced E12 variant did not affect layer-specific neurogenesis. While ChIP-Seq identified a big overlap for E12- and E47-specific binding sites in embryonic NSCs, including sites at the cyclin-dependent kinase inhibitor (CDKI) Cdkn1c gene locus, RNA-Seq revealed a unique transcriptional regulation by each splice variant. E47 activated the expression of the CDKI Cdkn1c through binding to a distal enhancer. Finally, overexpression of E47 in embryonic NSCs in vitro impaired neurite outgrowth and E47 overexpression in vivo by in utero electroporation disturbed proper layer-specific neurogenesis and upregulated p57(KIP2) expression. Overall, this study identified E2A target genes in embryonic NSCs and demonstrates that E47 regulates neuronal differentiation via p57(KIP2)."}],"month":"10","intvolume":" 144","quality_controlled":"1","scopus_import":"1","publisher":"Company of Biologists"},{"_id":"621","status":"public","pubrep_id":"928","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"ddc":["571","610"],"date_updated":"2024-02-14T12:02:08Z","department":[{"_id":"SiHi"}],"file_date_updated":"2020-07-14T12:47:24Z","oa_version":"Published Version","pmid":1,"abstract":[{"text":"The mammalian cerebral cortex is responsible for higher cognitive functions such as perception, consciousness, and acquiring and processing information. The neocortex is organized into six distinct laminae, each composed of a rich diversity of cell types which assemble into highly complex cortical circuits. Radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. Here, we discuss recent discoveries emerging from clonal lineage analysis at the single RGP cell level that provide us with an inaugural quantitative framework of RGP lineage progression. We further discuss the importance of the relative contribution of intrinsic gene functions and non-cell-autonomous or community effects in regulating RGP proliferation behavior and lineage progression.","lang":"eng"}],"month":"12","intvolume":" 591","scopus_import":"1","file":[{"file_id":"5211","checksum":"a46dadc84e0c28d389dd3e9e954464db","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2018-12-12T10:16:24Z","file_name":"IST-2018-928-v1+1_Beattie_et_al-2017-FEBS_Letters.pdf","date_updated":"2020-07-14T12:47:24Z","file_size":644149,"creator":"system"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["00145793"]},"publication_status":"published","volume":591,"issue":"24","ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc/4.0/","project":[{"name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014","_id":"25D7962E-B435-11E9-9278-68D0E5697425"},{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Beattie RJ, Hippenmeyer S. 2017. Mechanisms of radial glia progenitor cell lineage progression. FEBS letters. 591(24), 3993–4008.","chicago":"Beattie, Robert J, and Simon Hippenmeyer. “Mechanisms of Radial Glia Progenitor Cell Lineage Progression.” FEBS Letters. Wiley-Blackwell, 2017. https://doi.org/10.1002/1873-3468.12906.","short":"R.J. Beattie, S. Hippenmeyer, FEBS Letters 591 (2017) 3993–4008.","ieee":"R. J. Beattie and S. Hippenmeyer, “Mechanisms of radial glia progenitor cell lineage progression,” FEBS letters, vol. 591, no. 24. Wiley-Blackwell, pp. 3993–4008, 2017.","apa":"Beattie, R. J., & Hippenmeyer, S. (2017). Mechanisms of radial glia progenitor cell lineage progression. FEBS Letters. Wiley-Blackwell. https://doi.org/10.1002/1873-3468.12906","ama":"Beattie RJ, Hippenmeyer S. Mechanisms of radial glia progenitor cell lineage progression. FEBS letters. 2017;591(24):3993-4008. doi:10.1002/1873-3468.12906","mla":"Beattie, Robert J., and Simon Hippenmeyer. “Mechanisms of Radial Glia Progenitor Cell Lineage Progression.” FEBS Letters, vol. 591, no. 24, Wiley-Blackwell, 2017, pp. 3993–4008, doi:10.1002/1873-3468.12906."},"title":"Mechanisms of radial glia progenitor cell lineage progression","publist_id":"7183","author":[{"id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","first_name":"Robert J","last_name":"Beattie","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"Yes (in subscription journal)","external_id":{"pmid":["29121403"]},"quality_controlled":"1","publisher":"Wiley-Blackwell","oa":1,"day":"01","publication":"FEBS letters","has_accepted_license":"1","year":"2017","date_published":"2017-12-01T00:00:00Z","doi":"10.1002/1873-3468.12906","date_created":"2018-12-11T11:47:32Z","page":"3993 - 4008"},{"oa_version":"None","intvolume":" 19","month":"08","publisher":"Elsevier","quality_controlled":"1","language":[{"iso":"eng"}],"publication":"Cell Stem Cell","day":"16","year":"2016","publication_status":"published","publication_identifier":{"issn":["1934-5909"]},"date_created":"2019-11-28T13:09:09Z","doi":"10.1016/j.stem.2016.07.003","issue":"5","date_published":"2016-08-16T00:00:00Z","volume":19,"page":"653-662","_id":"7141","status":"public","type":"journal_article","article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","extern":"1","citation":{"chicago":"Rolando, Chiara, Andrea Erni, Alice Grison, Robert J Beattie, Anna Engler, Paul J. Gokhale, Marta Milo, Thomas Wegleiter, Sebastian Jessberger, and Verdon Taylor. “Multipotency of Adult Hippocampal NSCs in Vivo Is Restricted by Drosha/NFIB.” Cell Stem Cell. Elsevier, 2016. https://doi.org/10.1016/j.stem.2016.07.003.","ista":"Rolando C, Erni A, Grison A, Beattie RJ, Engler A, Gokhale PJ, Milo M, Wegleiter T, Jessberger S, Taylor V. 2016. Multipotency of adult hippocampal NSCs in vivo is restricted by Drosha/NFIB. Cell Stem Cell. 19(5), 653–662.","mla":"Rolando, Chiara, et al. “Multipotency of Adult Hippocampal NSCs in Vivo Is Restricted by Drosha/NFIB.” Cell Stem Cell, vol. 19, no. 5, Elsevier, 2016, pp. 653–62, doi:10.1016/j.stem.2016.07.003.","short":"C. Rolando, A. Erni, A. Grison, R.J. Beattie, A. Engler, P.J. Gokhale, M. Milo, T. Wegleiter, S. Jessberger, V. Taylor, Cell Stem Cell 19 (2016) 653–662.","ieee":"C. Rolando et al., “Multipotency of adult hippocampal NSCs in vivo is restricted by Drosha/NFIB,” Cell Stem Cell, vol. 19, no. 5. Elsevier, pp. 653–662, 2016.","apa":"Rolando, C., Erni, A., Grison, A., Beattie, R. J., Engler, A., Gokhale, P. J., … Taylor, V. (2016). Multipotency of adult hippocampal NSCs in vivo is restricted by Drosha/NFIB. Cell Stem Cell. Elsevier. https://doi.org/10.1016/j.stem.2016.07.003","ama":"Rolando C, Erni A, Grison A, et al. Multipotency of adult hippocampal NSCs in vivo is restricted by Drosha/NFIB. Cell Stem Cell. 2016;19(5):653-662. doi:10.1016/j.stem.2016.07.003"},"date_updated":"2021-01-12T08:12:00Z","title":"Multipotency of adult hippocampal NSCs in vivo is restricted by Drosha/NFIB","article_processing_charge":"No","author":[{"last_name":"Rolando","full_name":"Rolando, Chiara","first_name":"Chiara"},{"full_name":"Erni, Andrea","last_name":"Erni","first_name":"Andrea"},{"first_name":"Alice","last_name":"Grison","full_name":"Grison, Alice"},{"last_name":"Beattie","orcid":"0000-0002-8483-8753","full_name":"Beattie, Robert J","first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Engler","full_name":"Engler, Anna","first_name":"Anna"},{"full_name":"Gokhale, Paul J.","last_name":"Gokhale","first_name":"Paul J."},{"full_name":"Milo, Marta","last_name":"Milo","first_name":"Marta"},{"first_name":"Thomas","full_name":"Wegleiter, Thomas","last_name":"Wegleiter"},{"first_name":"Sebastian","full_name":"Jessberger, Sebastian","last_name":"Jessberger"},{"full_name":"Taylor, Verdon","last_name":"Taylor","first_name":"Verdon"}]}]