[{"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":"11336","file_date_updated":"2023-03-21T14:18:10Z","department":[{"_id":"SiHi"}],"date_updated":"2023-05-31T12:24:10Z","ddc":["570"],"scopus_import":"1","month":"11","intvolume":" 8","abstract":[{"lang":"eng","text":"The generation of a correctly-sized cerebral cortex with all-embracing neuronal and glial cell-type diversity critically depends on faithful radial glial progenitor (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene expression instructs RGP lineage progression is unknown. Here we utilize Mosaic Analysis with Double Markers (MADM)-based single cell technology and demonstrate that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts at the global tissue-wide level. Conversely, cortical astrocyte production and maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation. We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression that are dependent on complex interplays between intrinsic and tissue-wide properties. In a broader context our results imply a critical role for the genetic and cellular niche environment in neural stem cell behavior."}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"oa_version":"Published Version","issue":"44","related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/"}]},"volume":8,"ec_funded":1,"publication_identifier":{"issn":["2375-2548"]},"publication_status":"published","file":[{"creator":"patrickd","file_size":2973998,"date_updated":"2023-03-21T14:18:10Z","file_name":"sciadv.abq1263.pdf","date_created":"2023-03-21T14:18:10Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"checksum":"0117023e188542082ca6693cf39e7f03","file_id":"12742"}],"language":[{"iso":"eng"}],"project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"article_number":"abq1263","author":[{"first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"full_name":"Pauler, Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian"},{"last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer"}],"article_processing_charge":"No","title":"Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression","citation":{"chicago":"Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances. American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.abq1263.","ista":"Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. 8(44), abq1263.","mla":"Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances, vol. 8, no. 44, abq1263, American Association for the Advancement of Science, 2022, doi:10.1126/sciadv.abq1263.","apa":"Amberg, N., Pauler, F., Streicher, C., & Hippenmeyer, S. (2022). Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.abq1263","ama":"Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. 2022;8(44). doi:10.1126/sciadv.abq1263","short":"N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).","ieee":"N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression,” Science Advances, vol. 8, no. 44. American Association for the Advancement of Science, 2022."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","publisher":"American Association for the Advancement of Science","oa":1,"acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS Unit) and S. Gharagozlou for technical support. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A. received funding from the FWF Firnberg-Programm (T 1031). The work was supported by IST institutional funds and by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","doi":"10.1126/sciadv.abq1263","date_published":"2022-11-01T00:00:00Z","date_created":"2022-04-26T15:04:50Z","has_accepted_license":"1","year":"2022","day":"01","publication":"Science Advances"},{"acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","oa":1,"quality_controlled":"1","publisher":"Springer Nature","publication":"Nature Immunology","day":"11","year":"2022","isi":1,"has_accepted_license":"1","date_created":"2021-08-06T09:09:11Z","date_published":"2022-07-11T00:00:00Z","doi":"10.1038/s41590-022-01257-4","page":"1246-1255","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373","name":"Cellular navigation along spatial gradients"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255.","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature, 2022. https://doi.org/10.1038/s41590-022-01257-4.","ieee":"F. P. Assen et al., “Multitier mechanics control stromal adaptations in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature, pp. 1246–1255, 2022.","short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4","ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:10.1038/s41590-022-01257-4."},"title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","article_processing_charge":"No","external_id":{"isi":["000822975900002"]},"author":[{"full_name":"Assen, Frank P","orcid":"0000-0003-3470-6119","last_name":"Assen","first_name":"Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jun","last_name":"Abe","full_name":"Abe, Jun"},{"last_name":"Hons","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","first_name":"Miroslav"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert"},{"last_name":"Shamipour","full_name":"Shamipour, Shayan","first_name":"Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","last_name":"Kaufmann","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter"},{"last_name":"Costanzo","full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","first_name":"Tommaso","id":"D93824F4-D9BA-11E9-BB12-F207E6697425"},{"id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","last_name":"Krens","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996"},{"last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus"},{"first_name":"Burkhard","last_name":"Ludewig","full_name":"Ludewig, Burkhard"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg"},{"first_name":"Wolfgang","last_name":"Weninger","full_name":"Weninger, Wolfgang"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561"},{"last_name":"Luther","full_name":"Luther, Sanjiv A.","first_name":"Sanjiv A."},{"first_name":"Jens V.","full_name":"Stein, Jens V.","last_name":"Stein"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-4561-241X","last_name":"Sixt"}],"oa_version":"Published Version","abstract":[{"text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"intvolume":" 23","month":"07","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"date_created":"2022-07-25T07:11:32Z","file_name":"2022_NatureImmunology_Assen.pdf","creator":"dernst","date_updated":"2022-07-25T07:11:32Z","file_size":11475325,"file_id":"11642","checksum":"628e7b49809f22c75b428842efe70c68","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"publication_status":"published","publication_identifier":{"eissn":["1529-2916"],"issn":["1529-2908"]},"ec_funded":1,"volume":23,"_id":"9794","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)"},"article_type":"original","type":"journal_article","ddc":["570"],"date_updated":"2023-08-02T06:53:07Z","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"file_date_updated":"2022-07-25T07:11:32Z"},{"department":[{"_id":"SiHi"}],"file_date_updated":"2022-02-21T07:51:33Z","ddc":["570"],"date_updated":"2023-08-02T14:25:01Z","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)"},"_id":"10764","volume":13,"file":[{"date_created":"2022-02-21T07:51:33Z","file_name":"2022_NatureCommunications_Cheung.pdf","date_updated":"2022-02-21T07:51:33Z","file_size":7910519,"creator":"dernst","checksum":"51d580aff2327dd957946208a9749e1a","file_id":"10777","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["20411723"]},"publication_status":"published","month":"02","intvolume":" 13","scopus_import":"1","pmid":1,"oa_version":"Published Version","abstract":[{"text":"Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a fluorescent probe that tracks glutamine in live cells, which provides direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.","lang":"eng"}],"title":"Physiological synaptic activity and recognition memory require astroglial glutamine","author":[{"id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T","last_name":"Cheung","full_name":"Cheung, Giselle T"},{"first_name":"Danijela","last_name":"Bataveljic","full_name":"Bataveljic, Danijela"},{"first_name":"Josien","full_name":"Visser, Josien","last_name":"Visser"},{"last_name":"Kumar","full_name":"Kumar, Naresh","first_name":"Naresh"},{"first_name":"Julien","last_name":"Moulard","full_name":"Moulard, Julien"},{"first_name":"Glenn","last_name":"Dallérac","full_name":"Dallérac, Glenn"},{"first_name":"Daria","last_name":"Mozheiko","full_name":"Mozheiko, Daria"},{"first_name":"Astrid","full_name":"Rollenhagen, Astrid","last_name":"Rollenhagen"},{"first_name":"Pascal","full_name":"Ezan, Pascal","last_name":"Ezan"},{"full_name":"Mongin, Cédric","last_name":"Mongin","first_name":"Cédric"},{"first_name":"Oana","last_name":"Chever","full_name":"Chever, Oana"},{"first_name":"Alexis Pierre","last_name":"Bemelmans","full_name":"Bemelmans, Alexis Pierre"},{"full_name":"Lübke, Joachim","last_name":"Lübke","first_name":"Joachim"},{"first_name":"Isabelle","last_name":"Leray","full_name":"Leray, Isabelle"},{"first_name":"Nathalie","last_name":"Rouach","full_name":"Rouach, Nathalie"}],"external_id":{"pmid":["35136061"],"isi":["000757297200017"]},"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Cheung GT, Bataveljic D, Visser J, Kumar N, Moulard J, Dallérac G, Mozheiko D, Rollenhagen A, Ezan P, Mongin C, Chever O, Bemelmans AP, Lübke J, Leray I, Rouach N. 2022. Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. 13, 753.","chicago":"Cheung, Giselle T, Danijela Bataveljic, Josien Visser, Naresh Kumar, Julien Moulard, Glenn Dallérac, Daria Mozheiko, et al. “Physiological Synaptic Activity and Recognition Memory Require Astroglial Glutamine.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28331-7.","ama":"Cheung GT, Bataveljic D, Visser J, et al. Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. 2022;13. doi:10.1038/s41467-022-28331-7","apa":"Cheung, G. T., Bataveljic, D., Visser, J., Kumar, N., Moulard, J., Dallérac, G., … Rouach, N. (2022). Physiological synaptic activity and recognition memory require astroglial glutamine. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28331-7","short":"G.T. Cheung, D. Bataveljic, J. Visser, N. Kumar, J. Moulard, G. Dallérac, D. Mozheiko, A. Rollenhagen, P. Ezan, C. Mongin, O. Chever, A.P. Bemelmans, J. Lübke, I. Leray, N. Rouach, Nature Communications 13 (2022).","ieee":"G. T. Cheung et al., “Physiological synaptic activity and recognition memory require astroglial glutamine,” Nature Communications, vol. 13. Springer Nature, 2022.","mla":"Cheung, Giselle T., et al. “Physiological Synaptic Activity and Recognition Memory Require Astroglial Glutamine.” Nature Communications, vol. 13, 753, Springer Nature, 2022, doi:10.1038/s41467-022-28331-7."},"article_number":"753","date_published":"2022-02-08T00:00:00Z","doi":"10.1038/s41467-022-28331-7","date_created":"2022-02-20T23:01:30Z","day":"08","publication":"Nature Communications","isi":1,"has_accepted_license":"1","year":"2022","publisher":"Springer Nature","quality_controlled":"1","oa":1,"acknowledgement":"We thank D. Mazaud and. J. Cazères for technical assistance. This work was supported by grants from the European Research Council (Consolidator grant #683154) and European Union’s Horizon 2020 research and innovation program (Marie Sklodowska-Curie Innovative Training Networks, grant #722053, EU-GliaPhD) to N.R. and from FP7-PEOPLE Marie Curie Intra-European Fellowship for career development (grant #622289) to G.C."},{"_id":"11460","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","keyword":["Psychiatry and Mental health","Developmental Biology","Developmental Neuroscience","Molecular Biology"],"status":"public","date_updated":"2023-08-03T07:21:32Z","ddc":["570"],"file_date_updated":"2022-06-24T08:22:59Z","department":[{"_id":"SiHi"}],"abstract":[{"lang":"eng","text":"Background: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology.\r\nMethods: Here, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques.\r\nResults: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages.\r\nLimitations: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation.\r\nConclusions: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life."}],"oa_version":"Published Version","intvolume":" 13","month":"06","publication_status":"published","publication_identifier":{"issn":["2040-2392"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2022-06-24T08:22:59Z","file_name":"2022_MolecularAutism_Schaaf.pdf","date_updated":"2022-06-24T08:22:59Z","file_size":7552298,"creator":"dernst","checksum":"525d2618e855139089bbfc3e3d49d1b2","file_id":"11461","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1186/s13229-023-00539-4"}]},"volume":13,"article_number":"27","citation":{"chicago":"Schaaf, Zachary A., Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke, Simon Hippenmeyer, and Konstantinos S. Zarbalis. “WDFY3 Mutation Alters Laminar Position and Morphology of Cortical Neurons.” Molecular Autism. Springer Nature, 2022. https://doi.org/10.1186/s13229-022-00508-3.","ista":"Schaaf ZA, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis KS. 2022. WDFY3 mutation alters laminar position and morphology of cortical neurons. Molecular Autism. 13, 27.","mla":"Schaaf, Zachary A., et al. “WDFY3 Mutation Alters Laminar Position and Morphology of Cortical Neurons.” Molecular Autism, vol. 13, 27, Springer Nature, 2022, doi:10.1186/s13229-022-00508-3.","ieee":"Z. A. Schaaf et al., “WDFY3 mutation alters laminar position and morphology of cortical neurons,” Molecular Autism, vol. 13. Springer Nature, 2022.","short":"Z.A. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K.S. Zarbalis, Molecular Autism 13 (2022).","apa":"Schaaf, Z. A., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S., & Zarbalis, K. S. (2022). WDFY3 mutation alters laminar position and morphology of cortical neurons. Molecular Autism. Springer Nature. https://doi.org/10.1186/s13229-022-00508-3","ama":"Schaaf ZA, Tat L, Cannizzaro N, et al. WDFY3 mutation alters laminar position and morphology of cortical neurons. Molecular Autism. 2022;13. doi:10.1186/s13229-022-00508-3"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000814641400001"]},"article_processing_charge":"No","author":[{"first_name":"Zachary A.","full_name":"Schaaf, Zachary A.","last_name":"Schaaf"},{"first_name":"Lyvin","full_name":"Tat, Lyvin","last_name":"Tat"},{"last_name":"Cannizzaro","full_name":"Cannizzaro, Noemi","first_name":"Noemi"},{"last_name":"Green","full_name":"Green, Ralph","first_name":"Ralph"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Zarbalis","full_name":"Zarbalis, Konstantinos S.","first_name":"Konstantinos S."}],"title":"WDFY3 mutation alters laminar position and morphology of cortical neurons","acknowledgement":"This study was funded by NIMH R21MH115347 to KSZ. KSZ is further supported by Shriners Hospitals for Children.\r\nWe would like to thank Angelo Harlan de Crescenzo for early contributions to this project.","oa":1,"publisher":"Springer Nature","quality_controlled":"1","year":"2022","isi":1,"has_accepted_license":"1","publication":"Molecular Autism","day":"22","date_created":"2022-06-23T14:28:55Z","date_published":"2022-06-22T00:00:00Z","doi":"10.1186/s13229-022-00508-3"},{"author":[{"first_name":"Donovan J.","last_name":"Anderson","full_name":"Anderson, Donovan J."},{"full_name":"Pauler, Florian","last_name":"Pauler","first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Aaron","last_name":"Mckenna","full_name":"Mckenna, Aaron"},{"first_name":"Jay","last_name":"Shendure","full_name":"Shendure, Jay"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"last_name":"Horwitz","full_name":"Horwitz, Marshall S.","first_name":"Marshall S."}],"external_id":{"pmid":["35452605"],"isi":["000814124400002"]},"article_processing_charge":"No","title":"Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development","citation":{"apa":"Anderson, D. J., Pauler, F., Mckenna, A., Shendure, J., Hippenmeyer, S., & Horwitz, M. S. (2022). Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. Elsevier. https://doi.org/10.1016/j.cels.2022.03.006","ama":"Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. 2022;13(6):438-453.e5. doi:10.1016/j.cels.2022.03.006","ieee":"D. J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, and M. S. Horwitz, “Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development,” Cell Systems, vol. 13, no. 6. Elsevier, p. 438–453.e5, 2022.","short":"D.J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, Cell Systems 13 (2022) 438–453.e5.","mla":"Anderson, Donovan J., et al. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems, vol. 13, no. 6, Elsevier, 2022, p. 438–453.e5, doi:10.1016/j.cels.2022.03.006.","ista":"Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. 2022. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. 13(6), 438–453.e5.","chicago":"Anderson, Donovan J., Florian Pauler, Aaron Mckenna, Jay Shendure, Simon Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems. Elsevier, 2022. https://doi.org/10.1016/j.cels.2022.03.006."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","_id":"25D92700-B435-11E9-9278-68D0E5697425"}],"page":"438-453.e5","doi":"10.1016/j.cels.2022.03.006","date_published":"2022-06-15T00:00:00Z","date_created":"2022-06-19T22:01:57Z","isi":1,"year":"2022","day":"15","publication":"Cell Systems","quality_controlled":"1","publisher":"Elsevier","oa":1,"acknowledgement":"D.J.A. thanks Wayne K. Potts, Alan R. Rogers, Kristen Hawkes, Ryk Ward, and Jon Seger for inspiring a young undergraduate to apply evolutionary theory to intraorganism development. Supported by the Paul G. Allen Frontiers Group (University of Washington); NIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program 725780 LinPro to S.H.","department":[{"_id":"SiHi"}],"date_updated":"2023-08-03T07:19:43Z","article_type":"original","type":"journal_article","status":"public","_id":"11449","issue":"6","volume":13,"ec_funded":1,"publication_identifier":{"eissn":["2405-4720"],"issn":["2405-4712"]},"publication_status":"published","language":[{"iso":"eng"}],"scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cels.2022.03.006"}],"month":"06","intvolume":" 13","abstract":[{"text":"Mutations are acquired frequently, such that each cell's genome inscribes its history of cell divisions. Common genomic alterations involve loss of heterozygosity (LOH). LOH accumulates throughout the genome, offering large encoding capacity for inferring cell lineage. Using only single-cell RNA sequencing (scRNA-seq) of mouse brain cells, we found that LOH events spanning multiple genes are revealed as tracts of monoallelically expressed, constitutionally heterozygous single-nucleotide variants (SNVs). We simultaneously inferred cell lineage and marked developmental time points based on X chromosome inactivation and the total number of LOH events while identifying cell types from gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. This type of retrospective analysis could be incorporated into scRNA-seq pipelines and, compared with experimental approaches for determining lineage in model organisms, is applicable where genetic engineering is prohibited, such as humans.","lang":"eng"}],"pmid":1,"oa_version":"Published Version"},{"ddc":["570"],"date_updated":"2023-08-04T10:28:34Z","department":[{"_id":"SiHi"}],"file_date_updated":"2023-01-30T11:41:01Z","_id":"12283","keyword":["Cell Biology"],"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)"},"article_type":"original","type":"journal_article","language":[{"iso":"eng"}],"file":[{"file_id":"12461","checksum":"4346ed32cb7c89a8ca051c7da68a9a1c","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2023-01-30T11:41:01Z","file_name":"2022_JourCellBiology_Atherton.pdf","creator":"dernst","date_updated":"2023-01-30T11:41:01Z","file_size":13868733}],"publication_status":"published","publication_identifier":{"issn":["0021-9533"],"eissn":["1477-9137"]},"volume":135,"issue":"7","oa_version":"Published Version","pmid":1,"abstract":[{"text":"Neurons extend axons to form the complex circuitry of the mature brain. This depends on the coordinated response and continuous remodelling of the microtubule and F-actin networks in the axonal growth cone. Growth cone architecture remains poorly understood at nanoscales. We therefore investigated mouse hippocampal neuron growth cones using cryo-electron tomography to directly visualise their three-dimensional subcellular architecture with molecular detail. Our data showed that the hexagonal arrays of actin bundles that form filopodia penetrate and terminate deep within the growth cone interior. We directly observed the modulation of these and other growth cone actin bundles by alteration of individual F-actin helical structures. Microtubules with blunt, slightly flared or gently curved ends predominated in the growth cone, frequently contained lumenal particles and exhibited lattice defects. Investigation of the effect of absence of doublecortin, a neurodevelopmental cytoskeleton regulator, on growth cone cytoskeleton showed no major anomalies in overall growth cone organisation or in F-actin subpopulations. However, our data suggested that microtubules sustained more structural defects, highlighting the importance of microtubule integrity during growth cone migration.","lang":"eng"}],"intvolume":" 135","month":"04","scopus_import":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"apa":"Atherton, J., Stouffer, M. A., Francis, F., & Moores, C. A. (2022). Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.259234","ama":"Atherton J, Stouffer MA, Francis F, Moores CA. Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. Journal of Cell Science. 2022;135(7). doi:10.1242/jcs.259234","short":"J. Atherton, M.A. Stouffer, F. Francis, C.A. Moores, Journal of Cell Science 135 (2022).","ieee":"J. Atherton, M. A. Stouffer, F. Francis, and C. A. Moores, “Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography,” Journal of Cell Science, vol. 135, no. 7. The Company of Biologists, 2022.","mla":"Atherton, Joseph, et al. “Visualising the Cytoskeletal Machinery in Neuronal Growth Cones Using Cryo-Electron Tomography.” Journal of Cell Science, vol. 135, no. 7, 259234, The Company of Biologists, 2022, doi:10.1242/jcs.259234.","ista":"Atherton J, Stouffer MA, Francis F, Moores CA. 2022. Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. Journal of Cell Science. 135(7), 259234.","chicago":"Atherton, Joseph, Melissa A Stouffer, Fiona Francis, and Carolyn A. Moores. “Visualising the Cytoskeletal Machinery in Neuronal Growth Cones Using Cryo-Electron Tomography.” Journal of Cell Science. The Company of Biologists, 2022. https://doi.org/10.1242/jcs.259234."},"title":"Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography","article_processing_charge":"No","external_id":{"pmid":["35383828"],"isi":["000783840400010"]},"author":[{"first_name":"Joseph","full_name":"Atherton, Joseph","last_name":"Atherton"},{"full_name":"Stouffer, Melissa A","last_name":"Stouffer","id":"4C9372C4-F248-11E8-B48F-1D18A9856A87","first_name":"Melissa A"},{"last_name":"Francis","full_name":"Francis, Fiona","first_name":"Fiona"},{"full_name":"Moores, Carolyn A.","last_name":"Moores","first_name":"Carolyn A."}],"article_number":"259234","publication":"Journal of Cell Science","day":"01","year":"2022","has_accepted_license":"1","isi":1,"date_created":"2023-01-16T10:03:24Z","doi":"10.1242/jcs.259234","date_published":"2022-04-01T00:00:00Z","acknowledgement":"J.A. was supported by a grant from the Medical Research Council (MRC), UK (MR/R000352/1) to C.A.M. Cryo-EM data were collected on equipment funded by the Wellcome Trust, UK (079605/Z/06/Z) and the Biotechnology and Biological Sciences Research Council (BBSRC) UK (BB/L014211/1). F.F.’s salary and institute were supported by Inserm (Institut National de la Santé et de la Recherche Médicale), CNRS (Centre National de la Recherche Scientifique) and Sorbonne Université. F.F.’s group was particularly supported by Agence Nationale de la\r\nRecherche (ANR-16-CE16-0011-03) and Seventh Framework Programme (EUHEALTH-\r\n2013, DESIRE, N° 60253; also funding M.S.’s salary) and the European Cooperation in Science and Technology (COST Action CA16118). Open Access funding provided by Birkbeck College: Birkbeck University of London. Deposited in PMC for immediate release.","oa":1,"publisher":"The Company of Biologists","quality_controlled":"1"},{"pmid":1,"oa_version":"None","abstract":[{"text":"From a simple thought to a multicellular movement","lang":"eng"}],"intvolume":" 135","month":"04","scopus_import":"1","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["0021-9533"],"eissn":["1477-9137"]},"issue":"8","volume":135,"_id":"12282","status":"public","type":"journal_article","article_type":"letter_note","date_updated":"2023-08-04T10:28:04Z","department":[{"_id":"SiHi"},{"_id":"LeSa"}],"acknowledgement":"The authors want to thank Professors Carrie Bernecky, Tom Henzinger, Martin Loose and Gaia Novarino for accepting to be interviewed, thus giving significant contribution to the discussion that lead to this article.","publisher":"The Company of Biologists","quality_controlled":"1","publication":"Journal of Cell Science","day":"19","year":"2022","isi":1,"date_created":"2023-01-16T10:03:14Z","date_published":"2022-04-19T00:00:00Z","doi":"10.1242/jcs.260017","article_number":"260017","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ieee":"N. Amberg, M. A. Stouffer, and I. Vercellino, “Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole,” Journal of Cell Science, vol. 135, no. 8. The Company of Biologists, 2022.","short":"N. Amberg, M.A. Stouffer, I. Vercellino, Journal of Cell Science 135 (2022).","ama":"Amberg N, Stouffer MA, Vercellino I. Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. 2022;135(8). doi:10.1242/jcs.260017","apa":"Amberg, N., Stouffer, M. A., & Vercellino, I. (2022). Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.260017","mla":"Amberg, Nicole, et al. “Operation STEM Fatale – How an Equity, Diversity and Inclusion Initiative Has Brought Us to Reflect on the Current Challenges in Cell Biology and Science as a Whole.” Journal of Cell Science, vol. 135, no. 8, 260017, The Company of Biologists, 2022, doi:10.1242/jcs.260017.","ista":"Amberg N, Stouffer MA, Vercellino I. 2022. Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole. Journal of Cell Science. 135(8), 260017.","chicago":"Amberg, Nicole, Melissa A Stouffer, and Irene Vercellino. “Operation STEM Fatale – How an Equity, Diversity and Inclusion Initiative Has Brought Us to Reflect on the Current Challenges in Cell Biology and Science as a Whole.” Journal of Cell Science. The Company of Biologists, 2022. https://doi.org/10.1242/jcs.260017."},"title":"Operation STEM fatale – how an equity, diversity and inclusion initiative has brought us to reflect on the current challenges in cell biology and science as a whole","article_processing_charge":"No","external_id":{"isi":["000798123600015"],"pmid":["35438168"]},"author":[{"first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","last_name":"Amberg"},{"last_name":"Stouffer","full_name":"Stouffer, Melissa A","first_name":"Melissa A","id":"4C9372C4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Irene","id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87","last_name":"Vercellino","full_name":"Vercellino, Irene","orcid":"0000-0001-5618-3449"}]},{"title":"WDFY3 cell autonomously controls neuronal migration","department":[{"_id":"SiHi"}],"article_processing_charge":"No","external_id":{"pmid":["PPR454733"]},"author":[{"last_name":"Schaaf","full_name":"Schaaf, Zachary","first_name":"Zachary"},{"full_name":"Tat, Lyvin","last_name":"Tat","first_name":"Lyvin"},{"last_name":"Cannizzaro","full_name":"Cannizzaro, Noemi","first_name":"Noemi"},{"full_name":"Green, Ralph","last_name":"Green","first_name":"Ralph"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"last_name":"Zarbalis","full_name":"Zarbalis, K","first_name":"K"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2023-10-17T13:06:52Z","citation":{"ista":"Schaaf Z, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis K. WDFY3 cell autonomously controls neuronal migration. 10.21203/rs.3.rs-1316167/v1.","chicago":"Schaaf, Zachary, Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke, Simon Hippenmeyer, and K Zarbalis. “WDFY3 Cell Autonomously Controls Neuronal Migration.” Research Square, n.d. https://doi.org/10.21203/rs.3.rs-1316167/v1.","apa":"Schaaf, Z., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S., & Zarbalis, K. (n.d.). WDFY3 cell autonomously controls neuronal migration. Research Square. https://doi.org/10.21203/rs.3.rs-1316167/v1","ama":"Schaaf Z, Tat L, Cannizzaro N, et al. WDFY3 cell autonomously controls neuronal migration. doi:10.21203/rs.3.rs-1316167/v1","short":"Z. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K. Zarbalis, (n.d.).","ieee":"Z. Schaaf et al., “WDFY3 cell autonomously controls neuronal migration.” Research Square.","mla":"Schaaf, Zachary, et al. WDFY3 Cell Autonomously Controls Neuronal Migration. Research Square, doi:10.21203/rs.3.rs-1316167/v1."},"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":"preprint","_id":"10792","date_created":"2022-02-25T07:53:26Z","doi":"10.21203/rs.3.rs-1316167/v1","date_published":"2022-02-16T00:00:00Z","page":"30","language":[{"iso":"eng"}],"day":"16","year":"2022","publication_status":"submitted","publication_identifier":{"eissn":["2693-5015"]},"month":"02","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.21203/rs.3.rs-1316167/v1"}],"publisher":"Research Square","pmid":1,"oa_version":"Preprint","abstract":[{"text":"Background\r\nProper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology .\r\nMethods\r\nHere, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild type cells concomitantly in vivo using immunofluorescent techniques.\r\nResults\r\nWe revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. Limitations While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients.\r\nConclusions\r\nOur genetic approach revealed several cell autonomous requirements of Wdfy3 in neuronal development that could underly the pathogenic mechanisms of WDFY3-related ASD conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for Wdfy3 in regulating neuronal function and interconnectivity in postnatal life.","lang":"eng"}]},{"month":"07","intvolume":" 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","volume":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12726"},{"id":"14530","status":"public","relation":"dissertation_contains"}]},"issue":"1","ec_funded":1,"publication_identifier":{"eissn":["2753-149X"]},"publication_status":"published","file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"822e76e056c07099d1fb27d1ece5941b","file_id":"14061","success":1,"date_updated":"2023-08-16T08:00:30Z","file_size":4846551,"creator":"dernst","date_created":"2023-08-16T08:00:30Z","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf"}],"language":[{"iso":"eng"}],"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","_id":"10791","file_date_updated":"2023-08-16T08:00:30Z","department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"date_updated":"2023-11-30T10:55:12Z","ddc":["570"],"publisher":"Oxford Academic","quality_controlled":"1","oa":1,"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.","doi":"10.1093/oons/kvac009","date_published":"2022-07-07T00:00:00Z","date_created":"2022-02-25T07:52:11Z","has_accepted_license":"1","year":"2022","day":"07","publication":"Oxford Open Neuroscience","project":[{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"article_number":"kvac009","author":[{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen","full_name":"Hansen, Andi H"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian"},{"id":"3BE60946-F248-11E8-B48F-1D18A9856A87","first_name":"Michael","orcid":"0000-0003-4844-6311","full_name":"Riedl, Michael","last_name":"Riedl"},{"last_name":"Streicher","full_name":"Streicher, Carmen","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Heger","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena"},{"first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"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","full_name":"Tsai, Li Huei","last_name":"Tsai"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"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","title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","citation":{"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.","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.","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.","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).","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"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"publisher":"Cold Spring Harbor Laboratory","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.12.31.425016"}],"oa":1,"month":"01","abstract":[{"lang":"eng","text":"Acquired mutations are sufficiently frequent such that the genome of a single cell offers a record of its history of cell divisions. Among more common somatic genomic alterations are loss of heterozygosity (LOH). Large LOH events are potentially detectable in single cell RNA sequencing (scRNA-seq) datasets as tracts of monoallelic expression for constitutionally heterozygous single nucleotide variants (SNVs) located among contiguous genes. We identified runs of monoallelic expression, consistent with LOH, uniquely distributed throughout the genome in single cell brain cortex transcriptomes of F1 hybrids involving different inbred mouse strains. We then phylogenetically reconstructed single cell lineages and simultaneously identified cell types by corresponding gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. Compared to engineered recording systems, LOH events accumulate throughout the genome and across the lifetime of an organism, affording tremendous capacity for encoding lineage information and increasing resolution for later cell divisions. This approach can conceivably be computationally incorporated into scRNA-seq analysis and may be useful for organisms where genetic engineering is prohibitive, such as humans."}],"oa_version":"Preprint","acknowledgement":"We thank Bill Bolosky, Microsoft Research, for earlier work showing proof of concept in TCGA\r\nbulk RNA-seq data. Supported by the Paul G. Allen Frontiers Group (University of Washington);\r\nNIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b] life science call grant\r\n(C13-002) to SH, and the European Research Council (ERC) under the European Union’s\r\nHorizon 2020 research and innovation program 725780 LinPro to SH.","doi":"10.1101/2020.12.31.425016","date_published":"2021-01-01T00:00:00Z","date_created":"2021-02-04T07:23:23Z","ec_funded":1,"publication_status":"submitted","year":"2021","day":"01","publication":"bioRxiv","language":[{"iso":"eng"}],"type":"preprint","project":[{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"status":"public","_id":"9082","author":[{"full_name":"Anderson, Donovan J.","last_name":"Anderson","first_name":"Donovan J."},{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","last_name":"Pauler"},{"full_name":"McKenna, Aaron","last_name":"McKenna","first_name":"Aaron"},{"first_name":"Jay","last_name":"Shendure","full_name":"Shendure, Jay"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"},{"full_name":"Horwitz, Marshall S.","last_name":"Horwitz","first_name":"Marshall S."}],"article_processing_charge":"No","department":[{"_id":"SiHi"}],"title":"Simultaneous identification of brain cell type and lineage via single cell RNA sequencing","date_updated":"2021-02-04T07:29:53Z","citation":{"chicago":"Anderson, Donovan J., Florian Pauler, Aaron McKenna, Jay Shendure, Simon Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Identification of Brain Cell Type and Lineage via Single Cell RNA Sequencing.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.12.31.425016.","ista":"Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. bioRxiv, 10.1101/2020.12.31.425016.","mla":"Anderson, Donovan J., et al. “Simultaneous Identification of Brain Cell Type and Lineage via Single Cell RNA Sequencing.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.12.31.425016.","apa":"Anderson, D. J., Pauler, F., McKenna, A., Shendure, J., Hippenmeyer, S., & Horwitz, M. S. (n.d.). Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.12.31.425016","ama":"Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. bioRxiv. doi:10.1101/2020.12.31.425016","ieee":"D. J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, and M. S. Horwitz, “Simultaneous identification of brain cell type and lineage via single cell RNA sequencing,” bioRxiv. Cold Spring Harbor Laboratory.","short":"D.J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, BioRxiv (n.d.)."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"}]