[{"file_date_updated":"2023-01-30T11:41:01Z","date_updated":"2023-08-04T10:28:34Z","publication_identifier":{"issn":["0021-9533"],"eissn":["1477-9137"]},"volume":135,"year":"2022","issue":"7","keyword":["Cell Biology"],"type":"journal_article","month":"04","status":"public","date_published":"2022-04-01T00:00:00Z","title":"Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography","intvolume":"       135","citation":{"short":"J. Atherton, M.A. Stouffer, F. Francis, C.A. Moores, Journal of Cell Science 135 (2022).","mla":"Atherton, Joseph, et al. “Visualising the Cytoskeletal Machinery in Neuronal Growth Cones Using Cryo-Electron Tomography.” <i>Journal of Cell Science</i>, vol. 135, no. 7, 259234, The Company of Biologists, 2022, doi:<a href=\"https://doi.org/10.1242/jcs.259234\">10.1242/jcs.259234</a>.","ama":"Atherton J, Stouffer MA, Francis F, Moores CA. Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. <i>Journal of Cell Science</i>. 2022;135(7). doi:<a href=\"https://doi.org/10.1242/jcs.259234\">10.1242/jcs.259234</a>","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.","apa":"Atherton, J., Stouffer, M. A., Francis, F., &#38; Moores, C. A. (2022). Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. <i>Journal of Cell Science</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/jcs.259234\">https://doi.org/10.1242/jcs.259234</a>","chicago":"Atherton, Joseph, Melissa A Stouffer, Fiona Francis, and Carolyn A. Moores. “Visualising the Cytoskeletal Machinery in Neuronal Growth Cones Using Cryo-Electron Tomography.” <i>Journal of Cell Science</i>. The Company of Biologists, 2022. <a href=\"https://doi.org/10.1242/jcs.259234\">https://doi.org/10.1242/jcs.259234</a>.","ieee":"J. Atherton, M. A. Stouffer, F. Francis, and C. A. Moores, “Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography,” <i>Journal of Cell Science</i>, vol. 135, no. 7. The Company of Biologists, 2022."},"publication_status":"published","external_id":{"pmid":["35383828"],"isi":["000783840400010"]},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"lang":"eng","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."}],"scopus_import":"1","fulldoi":"https://doi.org/10.1242/jcs.259234","doi":"10.1242/jcs.259234","department":[{"_id":"SiHi"}],"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.","language":[{"iso":"eng"}],"day":"01","publication":"Journal of Cell Science","publisher":"The Company of Biologists","_id":"12283","oa_version":"Published Version","article_processing_charge":"No","oa":1,"has_accepted_license":"1","quality_controlled":"1","article_number":"259234","date_created":"2023-01-16T10:03:24Z","isi":1,"file":[{"date_created":"2023-01-30T11:41:01Z","file_name":"2022_JourCellBiology_Atherton.pdf","relation":"main_file","success":1,"date_updated":"2023-01-30T11:41:01Z","content_type":"application/pdf","file_id":"12461","access_level":"open_access","file_size":13868733,"creator":"dernst","checksum":"4346ed32cb7c89a8ca051c7da68a9a1c"}],"ddc":["570"],"article_type":"original","pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Atherton, Joseph","first_name":"Joseph","last_name":"Atherton"},{"id":"4C9372C4-F248-11E8-B48F-1D18A9856A87","last_name":"Stouffer","first_name":"Melissa A","full_name":"Stouffer, Melissa A"},{"full_name":"Francis, Fiona","first_name":"Fiona","last_name":"Francis"},{"first_name":"Carolyn A.","full_name":"Moores, Carolyn A.","last_name":"Moores"}]},{"doi":"10.1016/j.nbd.2022.105702","fulldoi":"https://doi.org/10.1016/j.nbd.2022.105702","scopus_import":"1","abstract":[{"text":"Human doublecortin (DCX) mutations are associated with severe brain malformations leading to aberrant neuron positioning (heterotopia), intellectual disability and epilepsy. DCX is a microtubule-associated protein which plays a key role during neurodevelopment in neuronal migration and differentiation. Dcx knockout (KO) mice show disorganized hippocampal pyramidal neurons. The CA2/CA3 pyramidal cell layer is present as two abnormal layers and disorganized CA3 KO pyramidal neurons are also more excitable than wild-type (WT) cells. To further identify abnormalities, we characterized Dcx KO hippocampal neurons at subcellular, molecular and ultrastructural levels. Severe defects were observed in mitochondria, affecting number and distribution. Also, the Golgi apparatus was visibly abnormal, increased in volume and abnormally organized. Transcriptome analyses from laser microdissected hippocampal tissue at postnatal day 60 (P60) highlighted organelle abnormalities. Ultrastructural studies of CA3 cells performed in P60 (young adult) and > 9 months (mature) tissue showed that organelle defects are persistent throughout life. Locomotor activity and fear memory of young and mature adults were also abnormal: Dcx KO mice consistently performed less well than WT littermates, with defects becoming more severe with age. Thus, we show that disruption of a neurodevelopmentally-regulated gene can lead to permanent organelle anomalies contributing to abnormal adult behavior.","lang":"eng"}],"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","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"},"external_id":{"pmid":["35339680"]},"publication_status":"published","acknowledgement":"We thank Sylvie Dumont for initial aid with laser microdissection and G. Martinez-Lorenzana for experimental help with electron microscopy. We thank the animal experimentation facility and cellular and tissue imaging platforms at the Institut du Fer à Moulin, supported also by the Région Ile de France and the FRC Rotary. The Francis lab was associated with the BioPsy Labex project and the Ecole des Neurosciences de Paris Ile-de-France (ENP) network. Our salaries and lab were supported by Inserm, the Centre national de la recherche scientifique (CNRS) and Sorbonne University. The Francis group obtained the following funding contributing to this project: the European Union (EU- HEALTH-2013, DESIRE, N° 60253), the JTC 2015 Neurodevelopmental Disorders affiliated with the French Agence National de la Recherche (for \r\nNEURON8-Full- 815-006 STEM-MCD, to FF), E-Rare-3, the ERA-Net for Research on Rare Diseases affiliated with the French ANR (ERARE18-049), the European Cooperation on Science and Technology (COST Action CA16118).","department":[{"_id":"SiHi"}],"year":"2022","volume":168,"publication_identifier":{"issn":["0969-9961"]},"date_updated":"2024-08-06T06:57:39Z","file_date_updated":"2024-08-06T06:54:24Z","citation":{"chicago":"Stouffer, Melissa A, R. Khalaf-Nazzal, C. Cifuentes-Diaz, G. Albertini, E. Bandet, G. Grannec, V. Lavilla, et al. “Doublecortin Mutation Leads to Persistent Defects in the Golgi Apparatus and Mitochondria in Adult Hippocampal Pyramidal Cells.” <i>Neurobiology of Disease</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.nbd.2022.105702\">https://doi.org/10.1016/j.nbd.2022.105702</a>.","ieee":"M. A. Stouffer <i>et al.</i>, “Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells,” <i>Neurobiology of Disease</i>, vol. 168. Elsevier, 2022.","ama":"Stouffer MA, Khalaf-Nazzal R, Cifuentes-Diaz C, et al. Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells. <i>Neurobiology of Disease</i>. 2022;168. doi:<a href=\"https://doi.org/10.1016/j.nbd.2022.105702\">10.1016/j.nbd.2022.105702</a>","ista":"Stouffer MA, Khalaf-Nazzal R, Cifuentes-Diaz C, Albertini G, Bandet E, Grannec G, Lavilla V, Deleuze J-F, Olaso R, Nosten-Bertrand M, Francis F. 2022. Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells. Neurobiology of Disease. 168, 105702.","apa":"Stouffer, M. A., Khalaf-Nazzal, R., Cifuentes-Diaz, C., Albertini, G., Bandet, E., Grannec, G., … Francis, F. (2022). Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells. <i>Neurobiology of Disease</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.nbd.2022.105702\">https://doi.org/10.1016/j.nbd.2022.105702</a>","short":"M.A. Stouffer, R. Khalaf-Nazzal, C. Cifuentes-Diaz, G. Albertini, E. Bandet, G. Grannec, V. Lavilla, J.-F. Deleuze, R. Olaso, M. Nosten-Bertrand, F. Francis, Neurobiology of Disease 168 (2022).","mla":"Stouffer, Melissa A., et al. “Doublecortin Mutation Leads to Persistent Defects in the Golgi Apparatus and Mitochondria in Adult Hippocampal Pyramidal Cells.” <i>Neurobiology of Disease</i>, vol. 168, 105702, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.nbd.2022.105702\">10.1016/j.nbd.2022.105702</a>."},"intvolume":"       168","title":"Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells","date_published":"2022-06-15T00:00:00Z","status":"public","month":"06","type":"journal_article","date_created":"2024-05-29T06:10:05Z","article_number":"105702","quality_controlled":"1","has_accepted_license":"1","oa":1,"author":[{"full_name":"Stouffer, Melissa A","first_name":"Melissa A","last_name":"Stouffer","id":"4C9372C4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Khalaf-Nazzal, R.","first_name":"R.","last_name":"Khalaf-Nazzal"},{"last_name":"Cifuentes-Diaz","full_name":"Cifuentes-Diaz, C.","first_name":"C."},{"last_name":"Albertini","first_name":"G.","full_name":"Albertini, G."},{"last_name":"Bandet","full_name":"Bandet, E.","first_name":"E."},{"last_name":"Grannec","full_name":"Grannec, G.","first_name":"G."},{"first_name":"V.","full_name":"Lavilla, V.","last_name":"Lavilla"},{"last_name":"Deleuze","first_name":"J.-F.","full_name":"Deleuze, J.-F."},{"full_name":"Olaso, R.","first_name":"R.","last_name":"Olaso"},{"last_name":"Nosten-Bertrand","first_name":"M.","full_name":"Nosten-Bertrand, M."},{"full_name":"Francis, F.","first_name":"F.","last_name":"Francis"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"article_type":"original","ddc":["570"],"file":[{"file_id":"17398","content_type":"application/pdf","date_updated":"2024-08-06T06:54:24Z","success":1,"relation":"main_file","file_name":"2022_NeurobioDisease_Stouffer.pdf","date_created":"2024-08-06T06:54:24Z","checksum":"b705d3d23d0b424ba29920be7ab64c23","creator":"dernst","file_size":8890818,"access_level":"open_access"}],"day":"15","language":[{"iso":"eng"}],"article_processing_charge":"Yes","_id":"17067","oa_version":"Published Version","publisher":"Elsevier","publication":"Neurobiology of Disease"},{"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","pmid":1,"author":[{"orcid":"0000-0001-8457-2572","first_name":"Giselle T","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","last_name":"Cheung"},{"full_name":"Bataveljic, Danijela","first_name":"Danijela","last_name":"Bataveljic"},{"last_name":"Visser","full_name":"Visser, Josien","first_name":"Josien"},{"last_name":"Kumar","full_name":"Kumar, Naresh","first_name":"Naresh"},{"first_name":"Julien","full_name":"Moulard, Julien","last_name":"Moulard"},{"last_name":"Dallérac","full_name":"Dallérac, Glenn","first_name":"Glenn"},{"full_name":"Mozheiko, Daria","first_name":"Daria","last_name":"Mozheiko"},{"first_name":"Astrid","full_name":"Rollenhagen, Astrid","last_name":"Rollenhagen"},{"full_name":"Ezan, Pascal","first_name":"Pascal","last_name":"Ezan"},{"full_name":"Mongin, Cédric","first_name":"Cédric","last_name":"Mongin"},{"last_name":"Chever","first_name":"Oana","full_name":"Chever, Oana"},{"first_name":"Alexis Pierre","full_name":"Bemelmans, Alexis Pierre","last_name":"Bemelmans"},{"first_name":"Joachim","full_name":"Lübke, Joachim","last_name":"Lübke"},{"full_name":"Leray, Isabelle","first_name":"Isabelle","last_name":"Leray"},{"full_name":"Rouach, Nathalie","first_name":"Nathalie","last_name":"Rouach"}],"isi":1,"file":[{"date_updated":"2022-02-21T07:51:33Z","content_type":"application/pdf","success":1,"file_id":"10777","file_name":"2022_NatureCommunications_Cheung.pdf","date_created":"2022-02-21T07:51:33Z","relation":"main_file","creator":"dernst","checksum":"51d580aff2327dd957946208a9749e1a","access_level":"open_access","file_size":7910519}],"ddc":["570"],"article_type":"original","article_number":"753","date_created":"2022-02-20T23:01:30Z","oa":1,"has_accepted_license":"1","quality_controlled":"1","publication":"Nature Communications","oa_version":"Published Version","_id":"10764","publisher":"Springer Nature","article_processing_charge":"No","day":"08","language":[{"iso":"eng"}],"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.","department":[{"_id":"SiHi"}],"abstract":[{"lang":"eng","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."}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"scopus_import":"1","fulldoi":"https://doi.org/10.1038/s41467-022-28331-7","doi":"10.1038/s41467-022-28331-7","publication_status":"published","external_id":{"pmid":["35136061"],"isi":["000757297200017"]},"date_published":"2022-02-08T00:00:00Z","title":"Physiological synaptic activity and recognition memory require astroglial glutamine","intvolume":"        13","citation":{"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.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-28331-7\">https://doi.org/10.1038/s41467-022-28331-7</a>.","ieee":"G. T. Cheung <i>et al.</i>, “Physiological synaptic activity and recognition memory require astroglial glutamine,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","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.","ama":"Cheung GT, Bataveljic D, Visser J, et al. Physiological synaptic activity and recognition memory require astroglial glutamine. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-28331-7\">10.1038/s41467-022-28331-7</a>","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. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-28331-7\">https://doi.org/10.1038/s41467-022-28331-7</a>","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).","mla":"Cheung, Giselle T., et al. “Physiological Synaptic Activity and Recognition Memory Require Astroglial Glutamine.” <i>Nature Communications</i>, vol. 13, 753, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-28331-7\">10.1038/s41467-022-28331-7</a>."},"month":"02","type":"journal_article","status":"public","publication_identifier":{"eissn":["2041-1723"]},"volume":13,"year":"2022","file_date_updated":"2022-02-21T07:51:33Z","date_updated":"2026-04-02T12:22:38Z"},{"date_published":"2022-07-07T00:00:00Z","title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","intvolume":"         1","citation":{"ieee":"A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1. Oxford University Press, 2022.","chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>. Oxford University Press, 2022. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>.","mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009, Oxford University Press, 2022, doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>.","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. <i>Oxford Open Neuroscience</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>","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.","ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1). doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>"},"month":"07","type":"journal_article","status":"public","publication_identifier":{"eissn":["2753-149X"]},"volume":1,"issue":"1","year":"2022","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"file_date_updated":"2023-08-16T08:00:30Z","date_updated":"2026-04-07T13:29:13Z","project":[{"call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular mechanisms of radial neuronal migration"}],"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.","department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"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"}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"fulldoi":"https://doi.org/10.1093/oons/kvac009","doi":"10.1093/oons/kvac009","publication_status":"published","external_id":{"pmid":["38596707"]},"publication":"Oxford Open Neuroscience","oa_version":"Published Version","_id":"10791","publisher":"Oxford University Press","article_processing_charge":"No","corr_author":"1","day":"07","language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12726"},{"status":"public","id":"14530","relation":"dissertation_contains"}]},"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Hansen, Andi H","first_name":"Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian"},{"full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311","first_name":"Michael","last_name":"Riedl","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Streicher, Carmen","first_name":"Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Anna-Magdalena","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","last_name":"Heger"},{"id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter","orcid":"0000-0002-7903-3010","first_name":"Susanne","full_name":"Laukoter, Susanne"},{"first_name":"Christoph M","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas","first_name":"Armel","full_name":"Nicolas, Armel"},{"id":"3A374330-F248-11E8-B48F-1D18A9856A87","last_name":"Hof","orcid":"0000-0003-2057-2754","first_name":"Björn","full_name":"Hof, Björn"},{"first_name":"Li Huei","full_name":"Tsai, Li Huei","last_name":"Tsai"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"}],"ec_funded":1,"file":[{"file_size":4846551,"access_level":"open_access","checksum":"822e76e056c07099d1fb27d1ece5941b","creator":"dernst","relation":"main_file","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","date_created":"2023-08-16T08:00:30Z","file_id":"14061","content_type":"application/pdf","date_updated":"2023-08-16T08:00:30Z","success":1}],"ddc":["570"],"article_type":"original","article_number":"kvac009","date_created":"2022-02-25T07:52:11Z","oa":1,"has_accepted_license":"1","quality_controlled":"1"},{"publication_identifier":{"eissn":["2693-5015"]},"day":"16","page":"30","year":"2022","language":[{"iso":"eng"}],"date_updated":"2023-10-17T13:06:52Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.21203/rs.3.rs-1316167/v1"}],"date_published":"2022-02-16T00:00:00Z","title":"WDFY3 cell autonomously controls neuronal migration","_id":"10792","publisher":"Research Square","oa_version":"Preprint","citation":{"ista":"Schaaf Z, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis K. WDFY3 cell autonomously controls neuronal migration. <a href=\"https://doi.org/10.21203/rs.3.rs-1316167/v1\">10.21203/rs.3.rs-1316167/v1</a>.","apa":"Schaaf, Z., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S., &#38; Zarbalis, K. (n.d.). WDFY3 cell autonomously controls neuronal migration. Research Square. <a href=\"https://doi.org/10.21203/rs.3.rs-1316167/v1\">https://doi.org/10.21203/rs.3.rs-1316167/v1</a>","ama":"Schaaf Z, Tat L, Cannizzaro N, et al. WDFY3 cell autonomously controls neuronal migration. doi:<a href=\"https://doi.org/10.21203/rs.3.rs-1316167/v1\">10.21203/rs.3.rs-1316167/v1</a>","mla":"Schaaf, Zachary, et al. <i>WDFY3 Cell Autonomously Controls Neuronal Migration</i>. Research Square, doi:<a href=\"https://doi.org/10.21203/rs.3.rs-1316167/v1\">10.21203/rs.3.rs-1316167/v1</a>.","short":"Z. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K. Zarbalis, (n.d.).","ieee":"Z. Schaaf <i>et al.</i>, “WDFY3 cell autonomously controls neuronal migration.” Research Square.","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. <a href=\"https://doi.org/10.21203/rs.3.rs-1316167/v1\">https://doi.org/10.21203/rs.3.rs-1316167/v1</a>."},"article_processing_charge":"No","month":"02","type":"preprint","status":"public","abstract":[{"lang":"eng","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."}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"fulldoi":"https://doi.org/10.21203/rs.3.rs-1316167/v1","doi":"10.21203/rs.3.rs-1316167/v1","date_created":"2022-02-25T07:53:26Z","oa":1,"publication_status":"submitted","external_id":{"pmid":["PPR454733"]},"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Schaaf","full_name":"Schaaf, Zachary","first_name":"Zachary"},{"last_name":"Tat","first_name":"Lyvin","full_name":"Tat, Lyvin"},{"full_name":"Cannizzaro, Noemi","first_name":"Noemi","last_name":"Cannizzaro"},{"first_name":"Ralph","full_name":"Green, Ralph","last_name":"Green"},{"full_name":"Rülicke, Thomas","first_name":"Thomas","last_name":"Rülicke"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Zarbalis","full_name":"Zarbalis, K","first_name":"K"}],"department":[{"_id":"SiHi"}]},{"language":[{"iso":"eng"}],"day":"11","corr_author":"1","publication":"Nature Immunology","article_processing_charge":"No","_id":"9794","publisher":"Springer Nature","oa_version":"Published Version","has_accepted_license":"1","oa":1,"quality_controlled":"1","date_created":"2021-08-06T09:09:11Z","file":[{"relation":"main_file","file_name":"2022_NatureImmunology_Assen.pdf","date_created":"2022-07-25T07:11:32Z","file_id":"11642","date_updated":"2022-07-25T07:11:32Z","content_type":"application/pdf","success":1,"file_size":11475325,"access_level":"open_access","checksum":"628e7b49809f22c75b428842efe70c68","creator":"dernst"}],"isi":1,"article_type":"original","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"ec_funded":1,"author":[{"orcid":"0000-0003-3470-6119","first_name":"Frank P","full_name":"Assen, Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","last_name":"Assen"},{"full_name":"Abe, Jun","first_name":"Jun","last_name":"Abe"},{"full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","first_name":"Miroslav","last_name":"Hons","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9843-3522","first_name":"Robert","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","last_name":"Shamipour","first_name":"Shayan","full_name":"Shamipour, Shayan"},{"full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","first_name":"Walter","last_name":"Kaufmann","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Costanzo","id":"D93824F4-D9BA-11E9-BB12-F207E6697425","full_name":"Costanzo, Tommaso","first_name":"Tommaso","orcid":"0000-0001-9732-3815"},{"last_name":"Krens","id":"2B819732-F248-11E8-B48F-1D18A9856A87","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","first_name":"Gabriel"},{"id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","last_name":"Brown","first_name":"Markus","full_name":"Brown, Markus"},{"last_name":"Ludewig","full_name":"Ludewig, Burkhard","first_name":"Burkhard"},{"full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Weninger, Wolfgang","first_name":"Wolfgang","last_name":"Weninger"},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","orcid":"0000-0001-6005-1561","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sanjiv A.","full_name":"Luther, Sanjiv A.","last_name":"Luther"},{"last_name":"Stein","full_name":"Stein, Jens V.","first_name":"Jens V."},{"full_name":"Sixt, Michael K","first_name":"Michael K","orcid":"0000-0002-4561-241X","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"file_date_updated":"2022-07-25T07:11:32Z","date_updated":"2025-06-11T13:52:43Z","volume":23,"publication_identifier":{"eissn":["1529-2916"],"issn":["1529-2908"]},"year":"2022","page":"1246-1255","status":"public","month":"07","type":"journal_article","title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","date_published":"2022-07-11T00:00:00Z","citation":{"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.","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>.","ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. 2022;23:1246-1255. doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>","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.","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. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>","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.” <i>Nature Immunology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>.","ieee":"F. P. Assen <i>et al.</i>, “Multitier mechanics control stromal adaptations in swelling lymph nodes,” <i>Nature Immunology</i>, vol. 23. Springer Nature, pp. 1246–1255, 2022."},"intvolume":"        23","external_id":{"isi":["000822975900002"],"pmid":["35817845"]},"publication_status":"published","scopus_import":"1","fulldoi":"https://doi.org/10.1038/s41590-022-01257-4","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"lang":"eng","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."}],"doi":"10.1038/s41590-022-01257-4","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"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.","project":[{"call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular Navigation Along Spatial Gradients"}]},{"year":"2021","issue":"4","volume":2,"publication_identifier":{"eissn":["2666-1667"]},"date_updated":"2025-04-15T08:23:07Z","file_date_updated":"2021-11-22T08:23:58Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"citation":{"ieee":"N. Amberg and S. Hippenmeyer, “Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers,” <i>STAR Protocols</i>, vol. 2, no. 4. Cell Press, 2021.","chicago":"Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate Genes in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>. Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.xpro.2021.100939\">https://doi.org/10.1016/j.xpro.2021.100939</a>.","mla":"Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate Genes in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>, vol. 2, no. 4, 100939, Cell Press, 2021, doi:<a href=\"https://doi.org/10.1016/j.xpro.2021.100939\">10.1016/j.xpro.2021.100939</a>.","short":"N. Amberg, S. Hippenmeyer, STAR Protocols 2 (2021).","ista":"Amberg N, Hippenmeyer S. 2021. Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. STAR Protocols. 2(4), 100939.","apa":"Amberg, N., &#38; Hippenmeyer, S. (2021). Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. <i>STAR Protocols</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.xpro.2021.100939\">https://doi.org/10.1016/j.xpro.2021.100939</a>","ama":"Amberg N, Hippenmeyer S. Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. <i>STAR Protocols</i>. 2021;2(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2021.100939\">10.1016/j.xpro.2021.100939</a>"},"intvolume":"         2","title":"Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers","date_published":"2021-11-10T00:00:00Z","status":"public","month":"11","type":"journal_article","doi":"10.1016/j.xpro.2021.100939","fulldoi":"https://doi.org/10.1016/j.xpro.2021.100939","scopus_import":"1","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling and introduction of a mutation of a gene of interest with single-cell resolution. This protocol highlights major steps for the generation of genetic mosaic tissue and the isolation and processing of respective tissues for downstream histological analysis. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).","lang":"eng"}],"publication_status":"published","acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical Facilities (PCF). We particularly thank Mohammad Goudarzi for assistance with photography of mouse perfusion and dissection. N.A. received support from FWF Firnberg-Programm (T 1031). This work was also supported by IST Austria institutional funds; FWF SFB F78 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","project":[{"grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"name":"Role of Eed in neural stem cell lineage progression","grant_number":"T01031","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"},{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"department":[{"_id":"SiHi"}],"day":"10","language":[{"iso":"eng"}],"article_processing_charge":"Yes","_id":"10321","oa_version":"Published Version","publisher":"Cell Press","publication":"STAR Protocols","corr_author":"1","date_created":"2021-11-21T23:01:28Z","article_number":"100939","quality_controlled":"1","has_accepted_license":"1","oa":1,"ec_funded":1,"author":[{"full_name":"Amberg, Nicole","first_name":"Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","article_type":"original","ddc":["573"],"file":[{"date_created":"2021-11-22T08:23:58Z","file_name":"2021_STARProtocols_Amberg.pdf","relation":"main_file","success":1,"content_type":"application/pdf","date_updated":"2021-11-22T08:23:58Z","file_id":"10329","access_level":"open_access","file_size":7309464,"creator":"cchlebak","checksum":"9e3f6d06bf583e7a8b6a9e9a60500a28"}]},{"article_processing_charge":"Yes","oa_version":"Published Version","_id":"10655","publisher":"Elsevier","publication":"Molecular Therapy - Methods and Clinical Development","corr_author":"1","day":"10","language":[{"iso":"eng"}],"author":[{"last_name":"Maes","id":"3838F452-F248-11E8-B48F-1D18A9856A87","full_name":"Maes, Margaret E","orcid":"0000-0001-9642-1085","first_name":"Margaret E"},{"last_name":"Wögenstein","first_name":"Gabriele M.","full_name":"Wögenstein, Gabriele M."},{"first_name":"Gloria","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","last_name":"Colombo"},{"id":"15240fc1-dbcd-11ea-9d1d-ac5a786425fd","last_name":"Casado Polanco","orcid":"0000-0001-8293-4568","first_name":"Raquel","full_name":"Casado Polanco, Raquel"},{"last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","first_name":"Sandra","orcid":"0000-0001-8635-0877"}],"ec_funded":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","article_type":"original","ddc":["570"],"file":[{"relation":"main_file","file_name":"2021_MolTherMethodsClinDev_Maes.pdf","date_created":"2022-01-24T07:43:09Z","file_id":"10657","content_type":"application/pdf","date_updated":"2022-01-24T07:43:09Z","success":1,"file_size":4794147,"access_level":"open_access","checksum":"77dc540e8011c5475031bdf6ccef20a6","creator":"cchlebak"}],"isi":1,"date_created":"2022-01-23T23:01:28Z","quality_controlled":"1","has_accepted_license":"1","oa":1,"citation":{"ieee":"M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert, “Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment,” <i>Molecular Therapy - Methods and Clinical Development</i>, vol. 23. Elsevier, pp. 210–224, 2021.","chicago":"Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” <i>Molecular Therapy - Methods and Clinical Development</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">https://doi.org/10.1016/j.omtm.2021.09.006</a>.","apa":"Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., &#38; Siegert, S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. <i>Molecular Therapy - Methods and Clinical Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">https://doi.org/10.1016/j.omtm.2021.09.006</a>","ama":"Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. <i>Molecular Therapy - Methods and Clinical Development</i>. 2021;23:210-224. doi:<a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">10.1016/j.omtm.2021.09.006</a>","ista":"Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. 23, 210–224.","mla":"Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” <i>Molecular Therapy - Methods and Clinical Development</i>, vol. 23, Elsevier, 2021, pp. 210–24, doi:<a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">10.1016/j.omtm.2021.09.006</a>.","short":"M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular Therapy - Methods and Clinical Development 23 (2021) 210–224."},"intvolume":"        23","title":"Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment","date_published":"2021-12-10T00:00:00Z","status":"public","month":"12","type":"journal_article","year":"2021","page":"210-224","volume":23,"publication_identifier":{"eissn":["2329-0501"]},"date_updated":"2025-04-14T07:41:46Z","file_date_updated":"2022-01-24T07:43:09Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 715571). The research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility, the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger and Michael Schunn for their animal colony management and support. We would also like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally, we would like to thank the Siegert team members for discussion about the manuscript.","project":[{"name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571","_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"department":[{"_id":"SaSi"},{"_id":"SiHi"}],"doi":"10.1016/j.omtm.2021.09.006","fulldoi":"https://doi.org/10.1016/j.omtm.2021.09.006","scopus_import":"1","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"lang":"eng","text":"Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.\r\n"}],"external_id":{"isi":["000748748500019"]},"publication_status":"published"},{"publication_status":"published","external_id":{"isi":["000632657400006"],"pmid":["33352118"]},"abstract":[{"lang":"eng","text":"The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis."}],"fulldoi":"https://doi.org/10.1016/j.neuron.2020.11.028","scopus_import":"1","doi":"10.1016/j.neuron.2020.11.028","department":[{"_id":"SiHi"}],"acknowledgement":"We thank M. Mishina for GluD2fl frozen embryos, T.C. Südhof and J.I. Morgan for Cbln1fl mice, L. Anderson for help in generating the MADM alleles, W. Joo for a previously unpublished construct, M. Yuzaki, K. Shen, J. Ding, and members of the Luo lab, including J.M. Kebschull, H. Li, J. Li, T. Li, C.M. McLaughlin, D. Pederick, J. Ren, D.C. Wang and C. Xu for discussions and critiques of the manuscript, and M. Yuzaki for supporting Y.H.T. during the final phase of this project. Y.H.T. was supported by a JSPS fellowship; S.A.S. was supported by a Stanford Graduate Fellowship and an NSF Predoctoral Fellowship; L.J. is supported by a Stanford Graduate Fellowship and an NSF Predoctoral Fellowship; M.J.W. is supported by a Burroughs Wellcome Fund CASI Award. This work was supported by an NIH grant (R01-NS050538) to L.L.; the European Research Council (ERC) under the European Union's Horizon 2020 research and innovations programme (No. 725780 LinPro) to S.H.; and Simons and James S. McDonnell Foundations and an NSF CAREER award to S.G.; L.L. is an HHMI investigator.","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780"}],"date_updated":"2025-09-10T09:58:28Z","publication_identifier":{"eissn":["1097-4199"]},"volume":109,"page":"P629-644.E8","year":"2021","issue":"4","month":"02","type":"journal_article","status":"public","date_published":"2021-02-17T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1101/2020.06.14.151258","open_access":"1"}],"title":"GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells","intvolume":"       109","citation":{"ama":"Takeo YH, Shuster SA, Jiang L, et al. GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. <i>Neuron</i>. 2021;109(4):P629-644.E8. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.11.028\">10.1016/j.neuron.2020.11.028</a>","ista":"Takeo YH, Shuster SA, Jiang L, Hu M, Luginbuhl DJ, Rülicke T, Contreras X, Hippenmeyer S, Wagner MJ, Ganguli S, Luo L. 2021. GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron. 109(4), P629–644.E8.","apa":"Takeo, Y. H., Shuster, S. A., Jiang, L., Hu, M., Luginbuhl, D. J., Rülicke, T., … Luo, L. (2021). GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.11.028\">https://doi.org/10.1016/j.neuron.2020.11.028</a>","short":"Y.H. Takeo, S.A. Shuster, L. Jiang, M. Hu, D.J. Luginbuhl, T. Rülicke, X. Contreras, S. Hippenmeyer, M.J. Wagner, S. Ganguli, L. Luo, Neuron 109 (2021) P629–644.E8.","mla":"Takeo, Yukari H., et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” <i>Neuron</i>, vol. 109, no. 4, Elsevier, 2021, p. P629–644.E8, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.11.028\">10.1016/j.neuron.2020.11.028</a>.","chicago":"Takeo, Yukari H., S. Andrew Shuster, Linnie Jiang, Miley Hu, David J. Luginbuhl, Thomas Rülicke, Ximena Contreras, et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” <i>Neuron</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.neuron.2020.11.028\">https://doi.org/10.1016/j.neuron.2020.11.028</a>.","ieee":"Y. H. Takeo <i>et al.</i>, “GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells,” <i>Neuron</i>, vol. 109, no. 4. Elsevier, p. P629–644.E8, 2021."},"oa":1,"quality_controlled":"1","date_created":"2020-09-21T11:59:47Z","isi":1,"article_type":"original","pmid":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","author":[{"first_name":"Yukari H.","full_name":"Takeo, Yukari H.","last_name":"Takeo"},{"first_name":"S. Andrew","full_name":"Shuster, S. Andrew","last_name":"Shuster"},{"first_name":"Linnie","full_name":"Jiang, Linnie","last_name":"Jiang"},{"last_name":"Hu","full_name":"Hu, Miley","first_name":"Miley"},{"last_name":"Luginbuhl","first_name":"David J.","full_name":"Luginbuhl, David J."},{"first_name":"Thomas","full_name":"Rülicke, Thomas","last_name":"Rülicke"},{"full_name":"Contreras, Ximena","first_name":"Ximena","last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Mark J.","full_name":"Wagner, Mark J.","last_name":"Wagner"},{"last_name":"Ganguli","full_name":"Ganguli, Surya","first_name":"Surya"},{"last_name":"Luo","first_name":"Liqun","full_name":"Luo, Liqun"}],"ec_funded":1,"language":[{"iso":"eng"}],"day":"17","publication":"Neuron","_id":"8544","publisher":"Elsevier","oa_version":"Preprint","article_processing_charge":"No"},{"file_date_updated":"2021-06-15T14:01:35Z","date_updated":"2026-04-02T11:52:30Z","volume":35,"publication_identifier":{"eissn":[" 2211-1247"]},"issue":"10","year":"2021","status":"public","month":"06","type":"journal_article","title":"Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum","date_published":"2021-06-08T00:00:00Z","citation":{"ieee":"T. Zhang <i>et al.</i>, “Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum,” <i>Cell Reports</i>, vol. 35, no. 10. Elsevier, 2021.","chicago":"Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand, Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” <i>Cell Reports</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">https://doi.org/10.1016/j.celrep.2021.109208</a>.","mla":"Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” <i>Cell Reports</i>, vol. 35, no. 10, 109208, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">10.1016/j.celrep.2021.109208</a>.","short":"T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen, C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell Reports 35 (2021).","apa":"Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan, B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">https://doi.org/10.1016/j.celrep.2021.109208</a>","ama":"Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. <i>Cell Reports</i>. 2021;35(10). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">10.1016/j.celrep.2021.109208</a>","ista":"Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. 35(10), 109208."},"intvolume":"        35","external_id":{"pmid":["34107249 "],"isi":["000659894300001"]},"publication_status":"published","fulldoi":"https://doi.org/10.1016/j.celrep.2021.109208","scopus_import":"1","abstract":[{"text":"Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated are unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, while intermediate levels of Notch activity generate inhibitory neurons, and daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors.","lang":"eng"}],"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","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"},"doi":"10.1016/j.celrep.2021.109208","department":[{"_id":"SiHi"}],"acknowledgement":"This work was supported by the program “Investissements d’avenir” ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under the European Union’s Horizon 2020 research and innovation programme grant agreement no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.” Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant, and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility, iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2 mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies. B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .","project":[{"grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of radial neuronal migration"}],"language":[{"iso":"eng"}],"related_material":{"link":[{"url":"https://doi.org/10.1101/2020.03.18.997205","relation":"earlier_version"}]},"day":"08","publication":"Cell Reports","article_processing_charge":"No","_id":"8546","publisher":"Elsevier","oa_version":"Published Version","has_accepted_license":"1","oa":1,"quality_controlled":"1","article_number":"109208","date_created":"2020-09-21T12:00:48Z","file":[{"file_size":8900385,"access_level":"open_access","checksum":"7def3d42ebc8f5675efb6f38819e3e2e","creator":"cziletti","relation":"main_file","date_created":"2021-06-15T14:01:35Z","file_name":"2021_CellReports_Zhang.pdf","file_id":"9554","success":1,"date_updated":"2021-06-15T14:01:35Z","content_type":"application/pdf"}],"isi":1,"article_type":"original","ddc":["570"],"pmid":1,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","ec_funded":1,"author":[{"first_name":"Tingting","full_name":"Zhang, Tingting","last_name":"Zhang"},{"full_name":"Liu, Tengyuan","first_name":"Tengyuan","last_name":"Liu"},{"last_name":"Mora","full_name":"Mora, Natalia","first_name":"Natalia"},{"full_name":"Guegan, Justine","first_name":"Justine","last_name":"Guegan"},{"last_name":"Bertrand","first_name":"Mathilde","full_name":"Bertrand, Mathilde"},{"last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","first_name":"Ximena"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","first_name":"Andi H","full_name":"Hansen, Andi H"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen"},{"first_name":"Marica","full_name":"Anderle, Marica","last_name":"Anderle"},{"last_name":"Danda","first_name":"Natasha","full_name":"Danda, Natasha"},{"full_name":"Tiberi, Luca","first_name":"Luca","last_name":"Tiberi"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon"},{"first_name":"Bassem A.","full_name":"Hassan, Bassem A.","last_name":"Hassan"}]},{"department":[{"_id":"SiHi"}],"acknowledgement":"Work in the I.L.H.-O. laboratory was supported by European Research Council Grant ERC-2015-CoG 681577 and German Research Foundation Ha 4466/10-1, Ha4466/11-1, Ha4466/12-1, SPP 1665, and SFB 936B5. Work in the S.J.B.B. laboratory was supported by Biotechnology and Biological Sciences Research Council BB/P003796/1, Medical Research Council MR/K004387/1 and MR/T033320/1, Wellcome Trust 215199/Z/19/Z and 102386/Z/13/Z, and John Fell Fund. Work in the S.H. laboratory was supported by European Research Council Grants ERC-2016-CoG 725780 LinPro and FWF SFB F78. This work was supported by National Institutes of Health Grant NIMH 1R01MH110553 to N.V.D.M.G. Work in the J.A.C. laboratory was supported by the Ludwig Family Foundation, Simons Foundation SFARI Research Award, and National Institutes of Health/National Institute of Mental Health R01 MH102365 and R01MH113852. The B.V. laboratory was supported by Whitehall Foundation 2017-12-73, National Science Foundation 1736028, National Institutes of Health, National Institute of General Medical Sciences R01GM134363-01, and Halıcıoğlu Data Science Institute Fellowship. This work was supported by the University of California San Diego School of Medicine.","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780"},{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"publication_status":"published","external_id":{"pmid":["33431633"],"isi":["000616763400002"]},"doi":"10.1523/jneurosci.1655-20.2020","abstract":[{"lang":"eng","text":"The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorders, so that one can identify targets amenable to therapeutic intervention."}],"fulldoi":"https://doi.org/10.1523/jneurosci.1655-20.2020","scopus_import":"1","type":"journal_article","month":"02","status":"public","intvolume":"        41","citation":{"ista":"Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, De Marco García NV, Cardin JA, Voytek B, Muotri AR. 2021. The logic of developing neocortical circuits in health and disease. The Journal of Neuroscience. 41(5), 813–822.","ama":"Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, et al. The logic of developing neocortical circuits in health and disease. <i>The Journal of Neuroscience</i>. 2021;41(5):813-822. doi:<a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">10.1523/jneurosci.1655-20.2020</a>","apa":"Hanganu-Opatz, I. L., Butt, S. J. B., Hippenmeyer, S., De Marco García, N. V., Cardin, J. A., Voytek, B., &#38; Muotri, A. R. (2021). The logic of developing neocortical circuits in health and disease. <i>The Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">https://doi.org/10.1523/jneurosci.1655-20.2020</a>","mla":"Hanganu-Opatz, Ileana L., et al. “The Logic of Developing Neocortical Circuits in Health and Disease.” <i>The Journal of Neuroscience</i>, vol. 41, no. 5, Society for Neuroscience, 2021, pp. 813–22, doi:<a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">10.1523/jneurosci.1655-20.2020</a>.","short":"I.L. Hanganu-Opatz, S.J.B. Butt, S. Hippenmeyer, N.V. De Marco García, J.A. Cardin, B. Voytek, A.R. Muotri, The Journal of Neuroscience 41 (2021) 813–822.","ieee":"I. L. Hanganu-Opatz <i>et al.</i>, “The logic of developing neocortical circuits in health and disease,” <i>The Journal of Neuroscience</i>, vol. 41, no. 5. Society for Neuroscience, pp. 813–822, 2021.","chicago":"Hanganu-Opatz, Ileana L., Simon J. B. Butt, Simon Hippenmeyer, Natalia V. De Marco García, Jessica A. Cardin, Bradley Voytek, and Alysson R. Muotri. “The Logic of Developing Neocortical Circuits in Health and Disease.” <i>The Journal of Neuroscience</i>. Society for Neuroscience, 2021. <a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">https://doi.org/10.1523/jneurosci.1655-20.2020</a>."},"date_published":"2021-02-03T00:00:00Z","title":"The logic of developing neocortical circuits in health and disease","date_updated":"2025-04-15T08:23:06Z","file_date_updated":"2022-05-27T06:59:55Z","page":"813-822","keyword":["General Neuroscience"],"issue":"5","year":"2021","publication_identifier":{"issn":["0270-6474"],"eissn":["1529-2401"]},"volume":41,"ddc":["570"],"article_type":"original","isi":1,"file":[{"file_id":"11414","date_updated":"2022-05-27T06:59:55Z","content_type":"application/pdf","success":1,"relation":"main_file","file_name":"2021_JourNeuroscience_Hanganu.pdf","date_created":"2022-05-27T06:59:55Z","checksum":"578fd7ed1a0aef74bce61bea2d987b33","creator":"dernst","file_size":1031150,"access_level":"open_access"}],"ec_funded":1,"author":[{"first_name":"Ileana L.","full_name":"Hanganu-Opatz, Ileana L.","last_name":"Hanganu-Opatz"},{"full_name":"Butt, Simon J. B.","first_name":"Simon J. B.","last_name":"Butt"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"},{"full_name":"De Marco García, Natalia V.","first_name":"Natalia V.","last_name":"De Marco García"},{"first_name":"Jessica A.","full_name":"Cardin, Jessica A.","last_name":"Cardin"},{"last_name":"Voytek","full_name":"Voytek, Bradley","first_name":"Bradley"},{"first_name":"Alysson R.","full_name":"Muotri, Alysson R.","last_name":"Muotri"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","pmid":1,"quality_controlled":"1","oa":1,"has_accepted_license":"1","date_created":"2021-02-03T12:23:51Z","publisher":"Society for Neuroscience","_id":"9073","oa_version":"Published Version","article_processing_charge":"No","publication":"The Journal of Neuroscience","language":[{"iso":"eng"}],"day":"03"},{"publication_identifier":{"issn":["0197-0186"]},"volume":145,"keyword":["Cell Biology","Cellular and Molecular Neuroscience"],"year":"2021","issue":"5","file_date_updated":"2021-08-11T12:30:38Z","date_updated":"2025-04-14T07:43:04Z","date_published":"2021-05-01T00:00:00Z","title":"Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond","intvolume":"       145","citation":{"mla":"Pauler, Florian, et al. “Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell Level in Brain and Beyond.” <i>Neurochemistry International</i>, vol. 145, no. 5, 104986, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.neuint.2021.104986\">10.1016/j.neuint.2021.104986</a>.","short":"F. Pauler, Q. Hudson, S. Laukoter, S. Hippenmeyer, Neurochemistry International 145 (2021).","ista":"Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. 2021. Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry International. 145(5), 104986.","ama":"Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. <i>Neurochemistry International</i>. 2021;145(5). doi:<a href=\"https://doi.org/10.1016/j.neuint.2021.104986\">10.1016/j.neuint.2021.104986</a>","apa":"Pauler, F., Hudson, Q., Laukoter, S., &#38; Hippenmeyer, S. (2021). Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. <i>Neurochemistry International</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuint.2021.104986\">https://doi.org/10.1016/j.neuint.2021.104986</a>","ieee":"F. Pauler, Q. Hudson, S. Laukoter, and S. Hippenmeyer, “Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond,” <i>Neurochemistry International</i>, vol. 145, no. 5. Elsevier, 2021.","chicago":"Pauler, Florian, Quanah Hudson, Susanne Laukoter, and Simon Hippenmeyer. “Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell Level in Brain and Beyond.” <i>Neurochemistry International</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.neuint.2021.104986\">https://doi.org/10.1016/j.neuint.2021.104986</a>."},"type":"journal_article","month":"05","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","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"},"abstract":[{"lang":"eng","text":"Genomic imprinting is an epigenetic mechanism that results in parental allele-specific expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental regulators and play pivotal roles in many biological processes such as nutrient transfer from the mother to offspring and neuronal development. Imprinted genes are also involved in human disease, including neurodevelopmental disorders, and often occur in clusters that are regulated by a common imprint control region (ICR). In extra-embryonic tissues ICRs can act over large distances, with the largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical imprinted expression that shows near exclusive maternal or paternal expression, widespread biased imprinted expression has been identified mainly in brain. In this review we discuss recent developments mapping cell type specific imprinted expression in extra-embryonic tissues and neocortex in the mouse. We highlight the advantages of using an inducible uniparental chromosome disomy (UPD) system to generate cells carrying either two maternal or two paternal copies of a specific chromosome to analyze the functional consequences of genomic imprinting. Mosaic Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant induction of UPD sparsely in specific cell types, and thus to over-express or suppress all imprinted genes on that chromosome. To illustrate the utility of this technique, we explain how MADM-induced UPD revealed new insights about the function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs led to identification of highly cell type specific phenotypes related to perturbed imprinted expression in the mouse neocortex. Finally, we give an outlook on how MADM could be used to probe cell type specific imprinted expression in other tissues in mouse, particularly in extra-embryonic tissues."}],"fulldoi":"https://doi.org/10.1016/j.neuint.2021.104986","scopus_import":"1","doi":"10.1016/j.neuint.2021.104986","publication_status":"published","external_id":{"isi":["000635575000005"],"pmid":["33600873"]},"project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780"},{"grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"}],"acknowledgement":"We thank Melissa Stouffer for critically reading the manuscript. This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung n[f + b] life science call grant (C13-002) 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.","department":[{"_id":"SiHi"}],"day":"01","language":[{"iso":"eng"}],"publication":"Neurochemistry International","publisher":"Elsevier","_id":"9188","oa_version":"Published Version","article_processing_charge":"Yes (via OA deal)","article_number":"104986","date_created":"2021-02-23T12:31:43Z","oa":1,"has_accepted_license":"1","quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"ec_funded":1,"author":[{"full_name":"Pauler, Florian","first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hudson","full_name":"Hudson, Quanah","first_name":"Quanah"},{"orcid":"0000-0002-7903-3010","first_name":"Susanne","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"isi":1,"file":[{"relation":"main_file","date_created":"2021-08-11T12:30:38Z","file_name":"2021_NCI_Pauler.pdf","file_id":"9883","success":1,"date_updated":"2021-08-11T12:30:38Z","content_type":"application/pdf","file_size":7083499,"access_level":"open_access","checksum":"c6d7a40089cd29e289f9b22e75768304","creator":"kschuh"}],"ddc":["570"],"article_type":"original"},{"file_date_updated":"2021-06-28T08:04:22Z","date_updated":"2026-04-02T13:55:23Z","publication_identifier":{"eissn":["2041-1723"]},"volume":12,"year":"2021","issue":"1","month":"07","type":"journal_article","status":"public","date_published":"2021-07-12T00:00:00Z","title":"Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3","intvolume":"        12","citation":{"short":"L. Santini, F. Halbritter, F. Titz-Teixeira, T. Suzuki, M. Asami, X. Ma, J. Ramesmayer, A. Lackner, N. Warr, F. Pauler, S. Hippenmeyer, E. Laue, M. Farlik, C. Bock, A. Beyer, A.C.F. Perry, M. Leeb, Nature Communications 12 (2021).","mla":"Santini, Laura, et al. “Genomic Imprinting in Mouse Blastocysts Is Predominantly Associated with H3K27me3.” <i>Nature Communications</i>, vol. 12, no. 1, 3804, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23510-4\">10.1038/s41467-021-23510-4</a>.","ama":"Santini L, Halbritter F, Titz-Teixeira F, et al. Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23510-4\">10.1038/s41467-021-23510-4</a>","ista":"Santini L, Halbritter F, Titz-Teixeira F, Suzuki T, Asami M, Ma X, Ramesmayer J, Lackner A, Warr N, Pauler F, Hippenmeyer S, Laue E, Farlik M, Bock C, Beyer A, Perry ACF, Leeb M. 2021. Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. Nature Communications. 12(1), 3804.","apa":"Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ma, X., … Leeb, M. (2021). Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23510-4\">https://doi.org/10.1038/s41467-021-23510-4</a>","chicago":"Santini, Laura, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki, Maki Asami, Xiaoyan Ma, Julia Ramesmayer, et al. “Genomic Imprinting in Mouse Blastocysts Is Predominantly Associated with H3K27me3.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23510-4\">https://doi.org/10.1038/s41467-021-23510-4</a>.","ieee":"L. Santini <i>et al.</i>, “Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021."},"publication_status":"published","external_id":{"isi":["000667248600005"]},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"lang":"eng","text":"In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation."}],"fulldoi":"https://doi.org/10.1038/s41467-021-23510-4","scopus_import":"1","doi":"10.1038/s41467-021-23510-4","department":[{"_id":"SiHi"}],"acknowledgement":"The authors thank Robert Feil and Anton Wutz for helpful discussions and comments, Samuel Collombet and Peter Fraser for sharing embryo TAD coordinates, and Andy Riddel at the Cambridge Stem Cell Institute and Thomas Sauer at the Max Perutz Laboratories FACS facility for flow-sorting. We thank the team of the Biomedical Sequencing Facility at the CeMM and the Vienna Biocenter Core Facilities (VBCF) for support with next-generation sequencing. We are grateful to animal care teams at the University of Bath and MRC Harwell. A.C.F.P. acknowledges support from the UK Medical Research Council (MR/N000080/1 and MR/N020294/1) and Biotechnology and Biological Sciences Research Council (BB/P009506/1). L.S. is part of the FWF doctoral programme SMICH and supported by an Austrian Academy of Sciences DOC Fellowship. M.L. is funded by a Vienna Research Group for Young Investigators grant (VRG14-006) by the Vienna Science and Technology Fund (WWTF) and by the Austrian Science Fund FWF (I3786 and P31334).","language":[{"iso":"eng"}],"day":"12","publication":"Nature Communications","oa_version":"Published Version","_id":"9601","publisher":"Springer Nature","article_processing_charge":"No","oa":1,"has_accepted_license":"1","quality_controlled":"1","article_number":"3804","date_created":"2021-06-27T22:01:46Z","isi":1,"file":[{"file_id":"9608","success":1,"content_type":"application/pdf","date_updated":"2021-06-28T08:04:22Z","relation":"main_file","date_created":"2021-06-28T08:04:22Z","file_name":"2021_NatureCommunications_Santini.pdf","checksum":"75dd89d09945185b2d14b2434a0bcb50","creator":"asandaue","file_size":2156554,"access_level":"open_access"}],"ddc":["570"],"article_type":"original","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","author":[{"last_name":"Santini","full_name":"Santini, Laura","first_name":"Laura"},{"last_name":"Halbritter","first_name":"Florian","full_name":"Halbritter, Florian"},{"last_name":"Titz-Teixeira","full_name":"Titz-Teixeira, Fabian","first_name":"Fabian"},{"full_name":"Suzuki, Toru","first_name":"Toru","last_name":"Suzuki"},{"first_name":"Maki","full_name":"Asami, Maki","last_name":"Asami"},{"full_name":"Ma, Xiaoyan","first_name":"Xiaoyan","last_name":"Ma"},{"last_name":"Ramesmayer","full_name":"Ramesmayer, Julia","first_name":"Julia"},{"first_name":"Andreas","full_name":"Lackner, Andreas","last_name":"Lackner"},{"first_name":"Nick","full_name":"Warr, Nick","last_name":"Warr"},{"full_name":"Pauler, Florian","first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"},{"last_name":"Laue","full_name":"Laue, Ernest","first_name":"Ernest"},{"first_name":"Matthias","full_name":"Farlik, Matthias","last_name":"Farlik"},{"full_name":"Bock, Christoph","first_name":"Christoph","last_name":"Bock"},{"full_name":"Beyer, Andreas","first_name":"Andreas","last_name":"Beyer"},{"first_name":"Anthony C.F.","full_name":"Perry, Anthony C.F.","last_name":"Perry"},{"last_name":"Leeb","first_name":"Martin","full_name":"Leeb, Martin"}]},{"quality_controlled":"1","oa":1,"has_accepted_license":"1","date_created":"2021-06-27T22:01:48Z","article_number":"109274","ddc":["570"],"article_type":"original","isi":1,"file":[{"file_name":"2021_CellReports_Contreras.pdf","date_created":"2021-06-28T14:06:24Z","relation":"main_file","content_type":"application/pdf","date_updated":"2021-06-28T14:06:24Z","success":1,"file_id":"9613","access_level":"open_access","file_size":7653149,"creator":"asandaue","checksum":"d49520fdcbbb5c2f883bddb67cee5d77"}],"author":[{"first_name":"Ximena","full_name":"Contreras, Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","last_name":"Contreras"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","orcid":"0000-0002-3183-8207","first_name":"Nicole","full_name":"Amberg, Nicole"},{"id":"70ADC922-B424-11E9-99E3-BA18E6697425","last_name":"Davaatseren","first_name":"Amarbayasgalan","full_name":"Davaatseren, Amarbayasgalan"},{"first_name":"Andi H","full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen"},{"id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87","last_name":"Sonntag","first_name":"Johanna","full_name":"Sonntag, Johanna"},{"last_name":"Andersen","full_name":"Andersen, Lill","first_name":"Lill"},{"last_name":"Bernthaler","full_name":"Bernthaler, Tina","first_name":"Tina"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen"},{"last_name":"Heger","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","full_name":"Heger, Anna-Magdalena","first_name":"Anna-Magdalena"},{"first_name":"Randy L.","full_name":"Johnson, Randy L.","last_name":"Johnson"},{"last_name":"Schwarz","full_name":"Schwarz, Lindsay A.","first_name":"Lindsay A."},{"first_name":"Liqun","full_name":"Luo, Liqun","last_name":"Luo"},{"first_name":"Thomas","full_name":"Rülicke, Thomas","last_name":"Rülicke"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"ec_funded":1,"pmid":1,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","related_material":{"link":[{"url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/","relation":"press_release","description":"News on IST Homepage"}]},"language":[{"iso":"eng"}],"day":"22","_id":"9603","oa_version":"Published Version","publisher":"Cell Press","article_processing_charge":"No","publication":"Cell Reports","publication_status":"published","external_id":{"pmid":["34161767"],"isi":["000664463600016"]},"doi":"10.1016/j.celrep.2021.109274","abstract":[{"text":"Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.","lang":"eng"}],"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","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"},"scopus_import":"1","fulldoi":"https://doi.org/10.1016/j.celrep.2021.109274","department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular mechanisms of radial neuronal migration"},{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"acknowledgement":"We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 to S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.","date_updated":"2026-04-02T14:04:28Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"file_date_updated":"2021-06-28T14:06:24Z","year":"2021","issue":"12","publication_identifier":{"eissn":["2211-1247"]},"volume":35,"type":"journal_article","month":"06","status":"public","intvolume":"        35","citation":{"apa":"Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>","ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. 2021;35(12). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>","ista":"Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274.","short":"X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen, T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo, T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).","mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>, vol. 35, no. 12, 109274, Cell Press, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>.","chicago":"Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>. Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>.","ieee":"X. Contreras <i>et al.</i>, “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” <i>Cell Reports</i>, vol. 35, no. 12. Cell Press, 2021."},"date_published":"2021-06-22T00:00:00Z","title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis"},{"language":[{"iso":"eng"}],"day":"23","article_processing_charge":"No","_id":"6995","oa_version":"Preprint","publisher":"Springer Nature","publication":"Nature Neuroscience","quality_controlled":"1","oa":1,"date_created":"2019-11-10T11:23:58Z","article_type":"review","OA_place":"publisher","isi":1,"author":[{"full_name":"Samarasinghe, Ranmal A.","first_name":"Ranmal A.","last_name":"Samarasinghe"},{"id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","last_name":"Miranda","first_name":"Osvaldo","orcid":"0000-0001-6618-6889","full_name":"Miranda, Osvaldo"},{"last_name":"Buth","full_name":"Buth, Jessie E.","first_name":"Jessie E."},{"first_name":"Simon","full_name":"Mitchell, Simon","last_name":"Mitchell"},{"full_name":"Ferando, Isabella","first_name":"Isabella","last_name":"Ferando"},{"full_name":"Watanabe, Momoko","first_name":"Momoko","last_name":"Watanabe"},{"first_name":"Arinnae","full_name":"Kurdian, Arinnae","last_name":"Kurdian"},{"last_name":"Golshani","full_name":"Golshani, Peyman","first_name":"Peyman"},{"last_name":"Plath","first_name":"Kathrin","full_name":"Plath, Kathrin"},{"last_name":"Lowry","first_name":"William E.","full_name":"Lowry, William E."},{"last_name":"Parent","first_name":"Jack M.","full_name":"Parent, Jack M."},{"first_name":"Istvan","full_name":"Mody, Istvan","last_name":"Mody"},{"last_name":"Novitch","first_name":"Bennett G.","full_name":"Novitch, Bennett G."}],"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2025-07-09T09:00:12Z","year":"2021","page":"32","volume":24,"publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"status":"public","month":"08","type":"journal_article","OA_type":"green","citation":{"chicago":"Samarasinghe, Ranmal A., Osvaldo Miranda, Jessie E. Buth, Simon Mitchell, Isabella Ferando, Momoko Watanabe, Arinnae Kurdian, et al. “Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids.” <i>Nature Neuroscience</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41593-021-00906-5\">https://doi.org/10.1038/s41593-021-00906-5</a>.","ieee":"R. A. Samarasinghe <i>et al.</i>, “Identification of neural oscillations and epileptiform changes in human brain organoids,” <i>Nature Neuroscience</i>, vol. 24. Springer Nature, p. 32, 2021.","ista":"Samarasinghe RA, Miranda O, Buth JE, Mitchell S, Ferando I, Watanabe M, Kurdian A, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG. 2021. Identification of neural oscillations and epileptiform changes in human brain organoids. Nature Neuroscience. 24, 32.","ama":"Samarasinghe RA, Miranda O, Buth JE, et al. Identification of neural oscillations and epileptiform changes in human brain organoids. <i>Nature Neuroscience</i>. 2021;24:32. doi:<a href=\"https://doi.org/10.1038/s41593-021-00906-5\">10.1038/s41593-021-00906-5</a>","apa":"Samarasinghe, R. A., Miranda, O., Buth, J. E., Mitchell, S., Ferando, I., Watanabe, M., … Novitch, B. G. (2021). Identification of neural oscillations and epileptiform changes in human brain organoids. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-021-00906-5\">https://doi.org/10.1038/s41593-021-00906-5</a>","short":"R.A. Samarasinghe, O. Miranda, J.E. Buth, S. Mitchell, I. Ferando, M. Watanabe, A. Kurdian, P. Golshani, K. Plath, W.E. Lowry, J.M. Parent, I. Mody, B.G. Novitch, Nature Neuroscience 24 (2021) 32.","mla":"Samarasinghe, Ranmal A., et al. “Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids.” <i>Nature Neuroscience</i>, vol. 24, Springer Nature, 2021, p. 32, doi:<a href=\"https://doi.org/10.1038/s41593-021-00906-5\">10.1038/s41593-021-00906-5</a>."},"intvolume":"        24","title":"Identification of neural oscillations and epileptiform changes in human brain organoids","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/820183"}],"date_published":"2021-08-23T00:00:00Z","external_id":{"isi":["000687516300001"],"pmid":["34426698 "]},"publication_status":"published","doi":"10.1038/s41593-021-00906-5","fulldoi":"https://doi.org/10.1038/s41593-021-00906-5","scopus_import":"1","abstract":[{"text":"Human brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.","lang":"eng"}],"department":[{"_id":"GradSch"},{"_id":"SiHi"}],"acknowledgement":"We thank S. Butler, T. Carmichael and members of the laboratory of B.G.N. for helpful discussions and comments on the manuscript; N. Vishlaghi and F. Turcios-Hernandez for technical assistance, and J. Lee, S.-K. Lee, H. Shinagawa and K. Yoshikawa for valuable reagents. We also thank the UCLA Eli and Edythe Broad Stem Cell Research Center (BSCRC) and Intellectual and Developmental Disabilities Research Center microscopy cores for access to imaging facilities. This work was supported by grants from the California Institute for Regenerative Medicine (CIRM) (DISC1-08819 to B.G.N.), the National Institute of Health (R01NS089817, R01DA051897 and P50HD103557 to B.G.N.; K08NS119747 to R.A.S.; K99HD096105 to M.W.; R01MH123922, R01MH121521 and P50HD103557 to M.J.G.; R01GM099134 to K.P.; R01NS103788 to W.E.L.; R01NS088571 to J.M.P.; R01NS030549 and R01AG050474 to I.M.), and research awards from the UCLA Jonsson Comprehensive Cancer Center and BSCRC Ablon Scholars Program (to B.G.N.), the BSCRC Innovation Program (to B.G.N., K.P. and W.E.L.), the UCLA BSCRC Steffy Brain Aging Research Fund (to B.G.N. and W.E.L.) and the UCLA Clinical and Translational Science Institute (to B.G.N.), Paul Allen Family Foundation Frontiers Group (to K.P. and W.E.L.), the March of Dimes Foundation (to W.E.L.) and the Simons Foundation Autism Research Initiative Bridge to Independence Program (to R.A.S. and M.J.G.). R.A.S. was also supported by the UCLA/NINDS Translational Neuroscience Training Grant (R25NS065723), a Research and Training Fellowship from the American Epilepsy Society, a Taking Flight Award from CURE Epilepsy and a Clinician Scientist training award from the UCLA BSCRC. J.E.B. was supported by the UCLA BSCRC Rose Hills Foundation Graduate Scholarship Training Program. M.W. was supported by postdoctoral training awards provided by the UCLA BSCRC and the Uehara Memorial Foundation. O.A.M. and A.K. were supported in part by the UCLA-California State University Northridge CIRM-Bridges training program (EDUC2-08411). We also acknowledge the support of the IDDRC Cells, Circuits and Systems Analysis, Microscopy and Genetics and Genomics Cores of the Semel Institute of Neuroscience at UCLA, which are supported by the NICHD (U54HD087101 and P50HD10355701). We lastly acknowledge support from a Quantitative and Computational Biosciences Collaboratory Postdoctoral Fellowship to S.M. and the Quantitative and Computational Biosciences Collaboratory community, directed by M. Pellegrini."},{"publication":"International Journal of Molecular Sciences","oa_version":"Published Version","_id":"9906","publisher":"MDPI","article_processing_charge":"Yes","language":[{"iso":"eng"}],"day":"04","isi":1,"file":[{"date_created":"2021-08-16T09:29:17Z","file_name":"2021_InternationalJournalOfMolecularSciences_Yotova.pdf","relation":"main_file","success":1,"content_type":"application/pdf","date_updated":"2021-08-16T09:29:17Z","file_id":"9922","access_level":"open_access","file_size":2646018,"creator":"asandaue","checksum":"be7f0042607ca60549cb27513c19c6af"}],"ddc":["570"],"article_type":"original","pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Yotova","full_name":"Yotova, Iveta","first_name":"Iveta"},{"last_name":"Hudson","full_name":"Hudson, Quanah J.","first_name":"Quanah J."},{"first_name":"Florian","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler"},{"last_name":"Proestling","first_name":"Katharina","full_name":"Proestling, Katharina"},{"last_name":"Haslinger","first_name":"Isabella","full_name":"Haslinger, Isabella"},{"last_name":"Kuessel","full_name":"Kuessel, Lorenz","first_name":"Lorenz"},{"first_name":"Alexandra","full_name":"Perricos, Alexandra","last_name":"Perricos"},{"last_name":"Husslein","full_name":"Husslein, Heinrich","first_name":"Heinrich"},{"full_name":"Wenzl, René","first_name":"René","last_name":"Wenzl"}],"oa":1,"has_accepted_license":"1","quality_controlled":"1","article_number":"8385","date_created":"2021-08-15T22:01:27Z","month":"08","type":"journal_article","status":"public","date_published":"2021-08-04T00:00:00Z","title":"LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line","intvolume":"        22","citation":{"ieee":"I. Yotova <i>et al.</i>, “LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line,” <i>International Journal of Molecular Sciences</i>, vol. 22, no. 16. MDPI, 2021.","chicago":"Yotova, Iveta, Quanah J. Hudson, Florian Pauler, Katharina Proestling, Isabella Haslinger, Lorenz Kuessel, Alexandra Perricos, Heinrich Husslein, and René Wenzl. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.” <i>International Journal of Molecular Sciences</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/ijms22168385\">https://doi.org/10.3390/ijms22168385</a>.","mla":"Yotova, Iveta, et al. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.” <i>International Journal of Molecular Sciences</i>, vol. 22, no. 16, 8385, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/ijms22168385\">10.3390/ijms22168385</a>.","short":"I. Yotova, Q.J. Hudson, F. Pauler, K. Proestling, I. Haslinger, L. Kuessel, A. Perricos, H. Husslein, R. Wenzl, International Journal of Molecular Sciences 22 (2021).","ista":"Yotova I, Hudson QJ, Pauler F, Proestling K, Haslinger I, Kuessel L, Perricos A, Husslein H, Wenzl R. 2021. LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. International Journal of Molecular Sciences. 22(16), 8385.","ama":"Yotova I, Hudson QJ, Pauler F, et al. LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. <i>International Journal of Molecular Sciences</i>. 2021;22(16). doi:<a href=\"https://doi.org/10.3390/ijms22168385\">10.3390/ijms22168385</a>","apa":"Yotova, I., Hudson, Q. J., Pauler, F., Proestling, K., Haslinger, I., Kuessel, L., … Wenzl, R. (2021). LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. <i>International Journal of Molecular Sciences</i>. MDPI. <a href=\"https://doi.org/10.3390/ijms22168385\">https://doi.org/10.3390/ijms22168385</a>"},"file_date_updated":"2021-08-16T09:29:17Z","date_updated":"2025-06-12T06:29:07Z","publication_identifier":{"eissn":["1422-0067"],"issn":["1661-6596"]},"volume":22,"issue":"16","year":"2021","department":[{"_id":"SiHi"}],"acknowledgement":"Open access funding provided by Medical University of Vienna. The authors would like to thank all the participants and health professionals involved in the present study. We want to thank our technical assistants Barbara Widmar and Matthias Witzmann-Stern for their diligent work and constant assistance. We would like to thank Simon Hippenmeyer for access to\r\nbioinformatic infrastructure and resources.","publication_status":"published","external_id":{"pmid":["34445100"],"isi":["000689147400001"]},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"text":"Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways.","lang":"eng"}],"fulldoi":"https://doi.org/10.3390/ijms22168385","scopus_import":"1","doi":"10.3390/ijms22168385"},{"type":"preprint","month":"01","status":"public","oa_version":"Preprint","_id":"9082","article_processing_charge":"No","citation":{"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,” <i>bioRxiv</i>. .","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.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2020.12.31.425016\">https://doi.org/10.1101/2020.12.31.425016</a>.","mla":"Anderson, Donovan J., et al. “Simultaneous Identification of Brain Cell Type and Lineage via Single Cell RNA Sequencing.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2020.12.31.425016\">10.1101/2020.12.31.425016</a>.","short":"D.J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, BioRxiv (n.d.).","apa":"Anderson, D. J., Pauler, F., McKenna, A., Shendure, J., Hippenmeyer, S., &#38; Horwitz, M. S. (n.d.). Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2020.12.31.425016\">https://doi.org/10.1101/2020.12.31.425016</a>","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, <a href=\"https://doi.org/10.1101/2020.12.31.425016\">10.1101/2020.12.31.425016</a>.","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. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.12.31.425016\">10.1101/2020.12.31.425016</a>"},"main_file_link":[{"url":"https://doi.org/10.1101/2020.12.31.425016","open_access":"1"}],"date_published":"2021-01-01T00:00:00Z","publication":"bioRxiv","title":"Simultaneous identification of brain cell type and lineage via single cell RNA sequencing","date_updated":"2026-07-06T12:46:11Z","das_tickbox":"1","language":[{"iso":"eng"}],"year":"2021","day":"01","department":[{"_id":"SiHi"}],"ec_funded":1,"author":[{"full_name":"Anderson, Donovan J.","first_name":"Donovan J.","last_name":"Anderson"},{"orcid":"0000-0002-7462-0048","first_name":"Florian","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler"},{"last_name":"McKenna","full_name":"McKenna, Aaron","first_name":"Aaron"},{"full_name":"Shendure, Jay","first_name":"Jay","last_name":"Shendure"},{"full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Horwitz","first_name":"Marshall S.","full_name":"Horwitz, Marshall S."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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.","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"publication_status":"submitted","oa":1,"doi":"10.1101/2020.12.31.425016","date_created":"2021-02-04T07:23:23Z","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."}],"fulldoi":"https://doi.org/10.1101/2020.12.31.425016"},{"date_created":"2021-08-06T09:08:25Z","quality_controlled":"1","oa":1,"author":[{"full_name":"Baldwin, Katherine T.","first_name":"Katherine T.","last_name":"Baldwin"},{"last_name":"Tan","full_name":"Tan, Christabel X.","first_name":"Christabel X."},{"first_name":"Samuel T.","full_name":"Strader, Samuel T.","last_name":"Strader"},{"first_name":"Changyu","full_name":"Jiang, Changyu","last_name":"Jiang"},{"first_name":"Justin T.","full_name":"Savage, Justin T.","last_name":"Savage"},{"full_name":"Elorza-Vidal, Xabier","first_name":"Xabier","last_name":"Elorza-Vidal"},{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","last_name":"Contreras","first_name":"Ximena","full_name":"Contreras, Ximena"},{"full_name":"Rülicke, Thomas","first_name":"Thomas","last_name":"Rülicke"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Raúl","full_name":"Estévez, Raúl","last_name":"Estévez"},{"first_name":"Ru-Rong","full_name":"Ji, Ru-Rong","last_name":"Ji"},{"full_name":"Eroglu, Cagla","first_name":"Cagla","last_name":"Eroglu"}],"ec_funded":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"article_type":"original","OA_place":"publisher","ddc":["570"],"isi":1,"day":"04","language":[{"iso":"eng"}],"article_processing_charge":"No","publisher":"Elsevier","_id":"9793","oa_version":"Published Version","publication":"Neuron","doi":"10.1016/j.neuron.2021.05.025","scopus_import":"1","fulldoi":"https://doi.org/10.1016/j.neuron.2021.05.025","abstract":[{"lang":"eng","text":"Astrocytes extensively infiltrate the neuropil to regulate critical aspects of synaptic development and function. This process is regulated by transcellular interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes coordinate developmental processes among one another to parse out the synaptic neuropil and form non-overlapping territories is unknown. Here we identify a molecular mechanism regulating astrocyte-astrocyte interactions during development to coordinate astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked, astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for territory and morphological complexity in the developing mouse cortex. Furthermore, conditional deletion of Hepacam from developing astrocytes significantly impairs gap junction coupling between astrocytes and disrupts the balance between synaptic excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy with subcortical cysts in humans. Therefore, our findings suggest that disruption of astrocyte self-organization mechanisms could be an underlying cause of neural pathology."}],"external_id":{"isi":["000692851900010"],"pmid":["34171291"]},"publication_status":"published","acknowledgement":"This work was supported by the National Institutes of Health (R01 DA047258 and R01 NS102237 to C.E., F32 NS100392 to K.T.B.) and the Holland-Trice Brain Research Award (to C.E.). K.T.B. was supported by postdoctoral fellowships from the Foerster-Bernstein Family and The Hartwell Foundation. The Hippenmeyer lab was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovations program (725780 LinPro) to S.H. R.E. was supported by Ministerio de Ciencia y Tecnología (RTI2018-093493-B-I00). We thank the Duke Light Microscopy Core Facility, the Duke Transgenic Mouse Facility, Dr. U. Schulte for assistance with proteomic experiments, and Dr. D. Silver for critical review of the manuscript. Cartoon elements of figure panels were created using BioRender.com.","project":[{"grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"department":[{"_id":"SiHi"}],"year":"2021","issue":"15","page":"2427-2442.e10","volume":109,"publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"date_updated":"2026-07-28T12:30:05Z","citation":{"chicago":"Baldwin, Katherine T., Christabel X. Tan, Samuel T. Strader, Changyu Jiang, Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, et al. “HepaCAM Controls Astrocyte Self-Organization and Coupling.” <i>Neuron</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.neuron.2021.05.025\">https://doi.org/10.1016/j.neuron.2021.05.025</a>.","ieee":"K. T. Baldwin <i>et al.</i>, “HepaCAM controls astrocyte self-organization and coupling,” <i>Neuron</i>, vol. 109, no. 15. Elsevier, p. 2427–2442.e10, 2021.","apa":"Baldwin, K. T., Tan, C. X., Strader, S. T., Jiang, C., Savage, J. T., Elorza-Vidal, X., … Eroglu, C. (2021). HepaCAM controls astrocyte self-organization and coupling. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2021.05.025\">https://doi.org/10.1016/j.neuron.2021.05.025</a>","ista":"Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras X, Rülicke T, Hippenmeyer S, Estévez R, Ji R-R, Eroglu C. 2021. HepaCAM controls astrocyte self-organization and coupling. Neuron. 109(15), 2427–2442.e10.","ama":"Baldwin KT, Tan CX, Strader ST, et al. HepaCAM controls astrocyte self-organization and coupling. <i>Neuron</i>. 2021;109(15):2427-2442.e10. doi:<a href=\"https://doi.org/10.1016/j.neuron.2021.05.025\">10.1016/j.neuron.2021.05.025</a>","short":"K.T. Baldwin, C.X. Tan, S.T. Strader, C. Jiang, J.T. Savage, X. Elorza-Vidal, X. Contreras, T. Rülicke, S. Hippenmeyer, R. Estévez, R.-R. Ji, C. Eroglu, Neuron 109 (2021) 2427–2442.e10.","mla":"Baldwin, Katherine T., et al. “HepaCAM Controls Astrocyte Self-Organization and Coupling.” <i>Neuron</i>, vol. 109, no. 15, Elsevier, 2021, p. 2427–2442.e10, doi:<a href=\"https://doi.org/10.1016/j.neuron.2021.05.025\">10.1016/j.neuron.2021.05.025</a>."},"intvolume":"       109","title":"HepaCAM controls astrocyte self-organization and coupling","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.neuron.2021.05.025"}],"date_published":"2021-08-04T00:00:00Z","status":"public","month":"08","type":"journal_article","OA_type":"free access"},{"date_updated":"2026-04-08T07:19:09Z","file_date_updated":"2022-09-03T22:30:04Z","year":"2021","keyword":["Neuronal migration","Non-cell-autonomous","Cell-autonomous","Neurodevelopmental disease"],"page":"182","publication_identifier":{"issn":["2663-337X"]},"status":"public","month":"09","type":"dissertation","citation":{"ista":"Hansen AH. 2021. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. Institute of Science and Technology Austria.","ama":"Hansen AH. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. 2021. doi:<a href=\"https://doi.org/10.15479/at:ista:9962\">10.15479/at:ista:9962</a>","apa":"Hansen, A. H. (2021). <i>Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:9962\">https://doi.org/10.15479/at:ista:9962</a>","short":"A.H. Hansen, Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration, Institute of Science and Technology Austria, 2021.","mla":"Hansen, Andi H. <i>Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration</i>. Institute of Science and Technology Austria, 2021, doi:<a href=\"https://doi.org/10.15479/at:ista:9962\">10.15479/at:ista:9962</a>.","chicago":"Hansen, Andi H. “Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration.” Institute of Science and Technology Austria, 2021. <a href=\"https://doi.org/10.15479/at:ista:9962\">https://doi.org/10.15479/at:ista:9962</a>.","ieee":"A. H. Hansen, “Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration,” Institute of Science and Technology Austria, 2021."},"title":"Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration","date_published":"2021-09-02T00:00:00Z","publication_status":"published","doi":"10.15479/at:ista:9962","fulldoi":"https://doi.org/10.15479/at:ista:9962","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"lang":"eng","text":"The brain is one of the largest and most complex organs and it is composed of billions of neurons that communicate together enabling e.g. consciousness. The cerebral cortex is the largest site of neural integration in the central nervous system. Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final position, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at certain steps during the overall migration process. Moreover, functional analysis of genetic mosaics (mutant neurons present in wild-type/heterozygote environment) using the MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. The interactions of cell-intrinsic (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely unknown. In part of this thesis work we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-cell-autonomous and/or community effects. The direct comparison of mutant neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively analyze non-cell-autonomous effects. Such analysis enable the high-resolution analysis of projection neuron migration dynamics in distinct environments with concomitant isolation of genomic and proteomic profiles. Using these experimental paradigms and in combination with computational modeling we show and characterize the nature of non-cell-autonomous effects to coordinate radial neuron migration. Furthermore, this thesis discusses recent developments in neurodevelopment with focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal migration."}],"department":[{"_id":"GradSch"},{"_id":"SiHi"}],"project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular mechanisms of radial neuronal migration"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"8569"},{"relation":"part_of_dissertation","status":"public","id":"960"}]},"language":[{"iso":"eng"}],"day":"02","degree_awarded":"PhD","corr_author":"1","article_processing_charge":"No","_id":"9962","publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","alternative_title":["ISTA Thesis"],"has_accepted_license":"1","oa":1,"date_created":"2021-08-29T12:36:50Z","OA_place":"publisher","supervisor":[{"orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"}],"ddc":["570"],"file":[{"relation":"source_file","date_created":"2021-08-30T09:17:39Z","file_name":"Thesis_Hansen.docx","file_id":"9971","date_updated":"2022-09-03T22:30:04Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":10629190,"embargo_to":"open_access","access_level":"closed","checksum":"66b56f5b988b233dc66a4f4b4fb2cdfe","creator":"ahansen"},{"embargo":"2022-09-02","relation":"main_file","date_created":"2021-08-30T09:29:44Z","file_name":"Thesis_Hansen_PDFA-1a.pdf","file_id":"9972","content_type":"application/pdf","date_updated":"2022-09-03T22:30:04Z","file_size":13457469,"access_level":"open_access","checksum":"204fa40321a1c6289b68c473634c4bf3","creator":"ahansen"}],"author":[{"first_name":"Andi H","full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd"},{"article_number":"51512","date_created":"2020-03-20T13:16:41Z","oa":1,"has_accepted_license":"1","quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"author":[{"last_name":"Moon","full_name":"Moon, Hyang Mi","first_name":"Hyang Mi"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"},{"full_name":"Luo, Liqun","first_name":"Liqun","last_name":"Luo"},{"last_name":"Wynshaw-Boris","first_name":"Anthony","full_name":"Wynshaw-Boris, Anthony"}],"isi":1,"file":[{"relation":"main_file","file_name":"2020_elife_Moon.pdf","date_created":"2020-09-24T07:03:20Z","file_id":"8567","content_type":"application/pdf","date_updated":"2020-09-24T07:03:20Z","success":1,"file_size":15089438,"access_level":"open_access","checksum":"396ceb2dd10b102ef4e699666b9342c3","creator":"dernst"}],"ddc":["570"],"article_type":"original","day":"11","language":[{"iso":"eng"}],"publication":"eLife","_id":"7593","publisher":"eLife Sciences Publications","oa_version":"Published Version","article_processing_charge":"No","abstract":[{"lang":"eng","text":"Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from Pafah1b1-deficient mutants. Pafah1b1-deficient neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with mislocalization of furrow-associated markers, associated with actomyosin dysfunction and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility is tightly controlled to execute proper daughter cell separation."}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"scopus_import":"1","fulldoi":"https://doi.org/10.7554/elife.51512","doi":"10.7554/elife.51512","publication_status":"published","external_id":{"isi":["000522835800001"],"pmid":["32159512"]},"department":[{"_id":"SiHi"}],"publication_identifier":{"issn":["2050-084X"]},"volume":9,"year":"2020","file_date_updated":"2020-09-24T07:03:20Z","date_updated":"2023-08-18T07:06:31Z","date_published":"2020-03-11T00:00:00Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/751958"}],"title":"LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility","intvolume":"         9","citation":{"mla":"Moon, Hyang Mi, et al. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” <i>ELife</i>, vol. 9, 51512, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.51512\">10.7554/elife.51512</a>.","short":"H.M. Moon, S. Hippenmeyer, L. Luo, A. Wynshaw-Boris, ELife 9 (2020).","ista":"Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. 2020. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. eLife. 9, 51512.","ama":"Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.51512\">10.7554/elife.51512</a>","apa":"Moon, H. M., Hippenmeyer, S., Luo, L., &#38; Wynshaw-Boris, A. (2020). LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.51512\">https://doi.org/10.7554/elife.51512</a>","ieee":"H. M. Moon, S. Hippenmeyer, L. Luo, and A. Wynshaw-Boris, “LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","chicago":"Moon, Hyang Mi, Simon Hippenmeyer, Liqun Luo, and Anthony Wynshaw-Boris. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.51512\">https://doi.org/10.7554/elife.51512</a>."},"type":"journal_article","month":"03","status":"public"}]