[{"quality_controlled":"1","issue":"12","external_id":{"isi":["000451324700010"]},"publisher":"Nature Publishing Group","article_processing_charge":"No","_id":"3","volume":21,"publication":"Nature Neuroscience","abstract":[{"lang":"eng","text":"SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder."}],"intvolume":"        21","language":[{"iso":"eng"}],"acknowledgement":"This work was supported by the Simons Foundation Autism Research Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.","status":"public","has_accepted_license":"1","year":"2018","publication_status":"published","isi":1,"publist_id":"8054","title":"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition","author":[{"last_name":"Deliu","orcid":"0000-0002-7370-5293","first_name":"Elena","full_name":"Deliu, Elena","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Arecco, Niccoló","last_name":"Arecco","first_name":"Niccoló"},{"full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","last_name":"Morandell"},{"orcid":"0000-0002-9033-9096","first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","full_name":"Dotter, Christoph"},{"last_name":"Contreras","first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena"},{"full_name":"Girardot, Charles","last_name":"Girardot","first_name":"Charles"},{"first_name":"Eva","last_name":"Käsper","full_name":"Käsper, Eva"},{"full_name":"Kozlova, Alena","id":"C50A9596-02D0-11E9-976E-E38CFE5CBC1D","first_name":"Alena","last_name":"Kozlova"},{"first_name":"Kasumi","orcid":"0000-0001-6060-4795","last_name":"Kishi","full_name":"Kishi, Kasumi","id":"3065DFC4-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-9529-4464","first_name":"Ilaria","last_name":"Chiaradia","full_name":"Chiaradia, Ilaria","id":"B6467F20-02D0-11E9-BDA5-E960C241894A"},{"full_name":"Noh, Kyung","last_name":"Noh","first_name":"Kyung"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"date_published":"2018-11-19T00:00:00Z","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"}],"fulldoi":"https://doi.org/10.1038/s41593-018-0266-2","citation":{"short":"E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot, E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience 21 (2018) 1717–1727.","chicago":"Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” <i>Nature Neuroscience</i>. Nature Publishing Group, 2018. <a href=\"https://doi.org/10.1038/s41593-018-0266-2\">https://doi.org/10.1038/s41593-018-0266-2</a>.","ista":"Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 21(12), 1717–1727.","mla":"Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” <i>Nature Neuroscience</i>, vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:<a href=\"https://doi.org/10.1038/s41593-018-0266-2\">10.1038/s41593-018-0266-2</a>.","apa":"Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot, C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. <i>Nature Neuroscience</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41593-018-0266-2\">https://doi.org/10.1038/s41593-018-0266-2</a>","ieee":"E. Deliu <i>et al.</i>, “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition,” <i>Nature Neuroscience</i>, vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.","ama":"Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. <i>Nature Neuroscience</i>. 2018;21(12):1717-1727. doi:<a href=\"https://doi.org/10.1038/s41593-018-0266-2\">10.1038/s41593-018-0266-2</a>"},"scopus_import":"1","oa":1,"day":"19","article_type":"original","file_date_updated":"2020-07-14T12:45:58Z","file":[{"access_level":"open_access","file_id":"6255","file_name":"2017_NatureNeuroscience_Deliu.pdf","file_size":8167169,"relation":"main_file","date_created":"2019-04-09T07:41:57Z","date_updated":"2020-07-14T12:45:58Z","creator":"dernst","content_type":"application/pdf","checksum":"60abd0f05b7cdc08a6b0ec460884084f"}],"ddc":["570"],"pubrep_id":"1071","oa_version":"Submitted Version","corr_author":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","month":"11","doi":"10.1038/s41593-018-0266-2","date_created":"2018-12-11T11:44:05Z","date_updated":"2026-09-12T22:30:07Z","type":"journal_article","department":[{"_id":"GaNo"},{"_id":"EdHa"}],"project":[{"grant_number":"401299","_id":"254BA948-B435-11E9-9278-68D0E5697425","name":"Probing development and reversibility of autism spectrum disorders"}],"page":"1717 - 1727","related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/","description":"News on IST Homepage"}],"record":[{"id":"6074","relation":"popular_science","status":"public"},{"id":"12364","status":"public","relation":"dissertation_contains"}]}},{"publist_id":"7434","publication_status":"published","year":"2018","has_accepted_license":"1","date_published":"2018-03-01T00:00:00Z","author":[{"id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","full_name":"Tarlungeanu, Dora-Clara","last_name":"Tarlungeanu","first_name":"Dora-Clara"}],"title":"The branched chain amino acids in autism spectrum disorders ","_id":"395","publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","degree_awarded":"PhD","alternative_title":["ISTA Thesis"],"language":[{"iso":"eng"}],"license":"https://creativecommons.org/licenses/by/4.0/","status":"public","abstract":[{"lang":"eng","text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. "}],"date_created":"2018-12-11T11:46:14Z","date_updated":"2026-04-08T14:15:20Z","doi":"10.15479/AT:ISTA:th_992","month":"03","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","corr_author":"1","ddc":["570","616"],"pubrep_id":"992","oa_version":"Published Version","related_material":{"record":[{"id":"1183","relation":"part_of_dissertation","status":"public"}]},"page":"88","project":[{"name":"Transmembrane Transporters in Health and Disease","grant_number":"F03523","_id":"25473368-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"department":[{"_id":"GaNo"}],"type":"dissertation","oa":1,"OA_place":"publisher","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"},"publication_identifier":{"issn":["2663-337X"]},"fulldoi":"https://doi.org/10.15479/AT:ISTA:th_992","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"}],"supervisor":[{"orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"citation":{"chicago":"Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum Disorders .” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th_992\">https://doi.org/10.15479/AT:ISTA:th_992</a>.","ista":"Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria.","short":"D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders , Institute of Science and Technology Austria, 2018.","mla":"Tarlungeanu, Dora-Clara. <i>The Branched Chain Amino Acids in Autism Spectrum Disorders </i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_992\">10.15479/AT:ISTA:th_992</a>.","apa":"Tarlungeanu, D.-C. (2018). <i>The branched chain amino acids in autism spectrum disorders </i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th_992\">https://doi.org/10.15479/AT:ISTA:th_992</a>","ieee":"D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders ,” Institute of Science and Technology Austria, 2018.","ama":"Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders . 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_992\">10.15479/AT:ISTA:th_992</a>"},"file":[{"access_level":"closed","embargo_to":"open_access","checksum":"9f5231c96e0ad945040841a8630232da","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"dernst","date_created":"2019-04-05T09:19:17Z","relation":"source_file","date_updated":"2021-02-11T23:30:15Z","file_size":43684035,"file_name":"2018_Thesis_Tarlungeanu_source.docx","file_id":"6217"},{"checksum":"0c33c370aa2010df5c552db57a6d01e9","content_type":"application/pdf","creator":"dernst","date_created":"2019-04-05T09:19:17Z","relation":"main_file","date_updated":"2021-02-11T11:17:16Z","embargo":"2018-03-15","file_name":"2018_Thesis_Tarlungeanu.pdf","file_size":30511532,"file_id":"6218","access_level":"open_access"}],"file_date_updated":"2021-02-11T23:30:15Z","day":"01"},{"alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","_id":"323","abstract":[{"lang":"eng","text":"In the here presented thesis, we explore the role of branched actin networks in cell migration and antigen presentation, the two most relevant processes in dendritic cell biology. Branched actin networks construct lamellipodial protrusions at the leading edge of migrating cells. These are typically seen as adhesive structures, which mediate force transduction to the extracellular matrix that leads to forward locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found that the resulting cells lack lamellipodial protrusions. Instead, depending on the maturation state, one or multiple filopodia were formed. By challenging these cells in a variety of migration assays we found that lamellipodial protrusions are dispensable for the locomotion of leukocytes and actually dampen the speed of migration. However, lamellipodia are critically required to negotiate complex environments that DCs experience while they travel to the next draining lymph node. Taken together our results suggest that leukocyte lamellipodia have rather a sensory- than a force transducing function. Furthermore, we show for the first time structure and dynamics of dendritic cell F-actin at the immunological synapse with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension, leading to an altered ultrastructure of the immunological synapse and severe T cell priming defects. These results point towards a previously unappreciated role of the cellular mechanics of dendritic cells in T cell activation. Additionally, we present a novel cell culture based system for the differentiation of dendritic cells from conditionally immortalized hematopoietic precursors. These precursor cells are genetically tractable via the CRISPR/Cas9 system while they retain their ability to differentiate into highly migratory dendritic cells and other immune cells. This will foster the study of all aspects of dendritic cell biology and beyond. "}],"acknowledgement":"First of all I would like to thank Michael Sixt for giving me the opportunity to work in \r\nhis group and for his support throughout the years. He is a truly inspiring person and \r\nthe  best  boss  one  can  imagine.  I  would  also  like  to  thank  all  current  and  past \r\nmembers of the Sixt group for their help and the great working atmosphere in the lab. \r\nIt is a true privilege to work with such a bright, funny and friendly group of people and \r\nI’m  proud  that  I  could  be  part  of  it.  Furthermore,  I  would  like  to  say  ‘thank  you’  to Daria Siekhaus for all the meetings and discussion we had throughout the years \r\nand to  Federica  Benvenuti  for  being  part  of  my  committee.  I  am  also  grateful  to  Jack \r\nMerrin  in  the  nanofabrication  facility  and  all  the  people  working  in  the  bioimaging-\r\n, the electron microscopy- and the preclinical facilities.","language":[{"iso":"eng"}],"status":"public","has_accepted_license":"1","year":"2018","publication_status":"published","publist_id":"7542","author":[{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","first_name":"Alexander F","last_name":"Leithner"}],"title":"Branched actin networks in dendritic cell biology","date_published":"2018-04-12T00:00:00Z","fulldoi":"https://doi.org/10.15479/AT:ISTA:th_998","supervisor":[{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt"}],"publication_identifier":{"issn":["2663-337X"]},"citation":{"mla":"Leithner, Alexander F. <i>Branched Actin Networks in Dendritic Cell Biology</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">10.15479/AT:ISTA:th_998</a>.","apa":"Leithner, A. F. (2018). <i>Branched actin networks in dendritic cell biology</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">https://doi.org/10.15479/AT:ISTA:th_998</a>","ieee":"A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute of Science and Technology Austria, 2018.","ama":"Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">10.15479/AT:ISTA:th_998</a>","chicago":"Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">https://doi.org/10.15479/AT:ISTA:th_998</a>.","ista":"Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute of Science and Technology Austria.","short":"A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute of Science and Technology Austria, 2018."},"acknowledged_ssus":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"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"},"oa":1,"day":"12","file_date_updated":"2021-02-11T23:30:17Z","file":[{"embargo_to":"open_access","access_level":"closed","creator":"dernst","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"d5e3edbac548c26c1fa43a4b37a54a4c","file_id":"6219","file_size":29027671,"file_name":"PhD_thesis_AlexLeithner_final_version.docx","date_created":"2019-04-05T09:23:11Z","date_updated":"2021-02-11T23:30:17Z","relation":"source_file"},{"access_level":"open_access","content_type":"application/pdf","creator":"dernst","checksum":"071f7476db29e41146824ebd0697cb10","file_name":"PhD_thesis_AlexLeithner.pdf","embargo":"2019-04-15","file_size":66045341,"file_id":"6220","date_updated":"2021-02-11T11:17:16Z","date_created":"2019-04-05T09:23:11Z","relation":"main_file"}],"pubrep_id":"998","oa_version":"Published Version","ddc":["571","599","610"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","corr_author":"1","month":"04","doi":"10.15479/AT:ISTA:th_998","date_created":"2018-12-11T11:45:49Z","date_updated":"2025-09-22T08:27:34Z","type":"dissertation","department":[{"_id":"MiSi"}],"page":"99","related_material":{"record":[{"id":"1321","status":"public","relation":"part_of_dissertation"}]}},{"publist_id":"6245","isi":1,"publication_status":"published","year":"2017","has_accepted_license":"1","date_published":"2017-01-17T00:00:00Z","author":[{"full_name":"Chen, Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","last_name":"Chen","first_name":"Chong"},{"first_name":"Itaru","last_name":"Arai","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","full_name":"Arai, Itaru"},{"full_name":"Satterield, Rachel","first_name":"Rachel","last_name":"Satterield"},{"full_name":"Young, Samuel","last_name":"Young","first_name":"Samuel"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804"}],"title":"Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse","_id":"1117","article_processing_charge":"No","publisher":"Cell Press","external_id":{"isi":["000396470600013"]},"issue":"3","quality_controlled":"1","language":[{"iso":"eng"}],"status":"public","intvolume":"        18","abstract":[{"text":"GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author","lang":"eng"}],"publication":"Cell Reports","volume":18,"date_created":"2018-12-11T11:50:14Z","date_updated":"2026-04-08T14:09:28Z","doi":"10.1016/j.celrep.2016.12.067","month":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pubrep_id":"751","ddc":["571"],"oa_version":"Published Version","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"324"}]},"project":[{"_id":"25C26B1E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P24909-B24","name":"Mechanisms of transmitter release at GABAergic synapses"},{"name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","call_identifier":"FP7","_id":"25C0F108-B435-11E9-9278-68D0E5697425","grant_number":"268548"}],"page":"723 - 736","department":[{"_id":"PeJo"}],"ec_funded":1,"type":"journal_article","scopus_import":"1","oa":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"},"fulldoi":"https://doi.org/10.1016/j.celrep.2016.12.067","citation":{"short":"C. Chen,  itaru Arai, R. Satterield, S. Young, P.M. Jonas, Cell Reports 18 (2017) 723–736.","chicago":"Chen, Chong, itaru Arai, Rachel Satterield, Samuel Young, and Peter M Jonas. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” <i>Cell Reports</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.celrep.2016.12.067\">https://doi.org/10.1016/j.celrep.2016.12.067</a>.","ista":"Chen C, Arai  itaru, Satterield R, Young S, Jonas PM. 2017. Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 18(3), 723–736.","apa":"Chen, C., Arai,  itaru, Satterield, R., Young, S., &#38; Jonas, P. M. (2017). Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2016.12.067\">https://doi.org/10.1016/j.celrep.2016.12.067</a>","mla":"Chen, Chong, et al. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” <i>Cell Reports</i>, vol. 18, no. 3, Cell Press, 2017, pp. 723–36, doi:<a href=\"https://doi.org/10.1016/j.celrep.2016.12.067\">10.1016/j.celrep.2016.12.067</a>.","ieee":"C. Chen,  itaru Arai, R. Satterield, S. Young, and P. M. Jonas, “Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse,” <i>Cell Reports</i>, vol. 18, no. 3. Cell Press, pp. 723–736, 2017.","ama":"Chen C, Arai  itaru, Satterield R, Young S, Jonas PM. Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. <i>Cell Reports</i>. 2017;18(3):723-736. doi:<a href=\"https://doi.org/10.1016/j.celrep.2016.12.067\">10.1016/j.celrep.2016.12.067</a>"},"publication_identifier":{"issn":["2211-1247"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"file":[{"content_type":"application/pdf","creator":"system","relation":"main_file","date_updated":"2018-12-12T10:16:09Z","date_created":"2018-12-12T10:16:09Z","file_name":"IST-2017-751-v1+1_1-s2.0-S2211124716317740-main.pdf","file_size":4427591,"file_id":"5195","access_level":"open_access"}],"file_date_updated":"2018-12-12T10:16:09Z","day":"17"},{"publist_id":"6244","isi":1,"publication_status":"published","year":"2017","has_accepted_license":"1","date_published":"2017-01-18T00:00:00Z","title":"Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo","author":[{"first_name":"Jian","last_name":"Gan","full_name":"Gan, Jian","id":"3614E438-F248-11E8-B48F-1D18A9856A87"},{"id":"2F9C5AC8-F248-11E8-B48F-1D18A9856A87","full_name":"Weng, Shih-Ming","first_name":"Shih-Ming","last_name":"Weng"},{"last_name":"Pernia-Andrade","first_name":"Alejandro","full_name":"Pernia-Andrade, Alejandro","id":"36963E98-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Csicsvari, Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5193-4036","first_name":"Jozsef L","last_name":"Csicsvari"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"}],"_id":"1118","article_processing_charge":"No","publisher":"Elsevier","external_id":{"isi":["000396428200010"]},"issue":"2","quality_controlled":"1","intvolume":"        93","language":[{"iso":"eng"}],"status":"public","abstract":[{"text":"Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo.","lang":"eng"}],"publication":"Neuron","volume":93,"date_updated":"2025-04-15T07:20:01Z","doi":"10.1016/j.neuron.2016.12.018","date_created":"2018-12-11T11:50:15Z","month":"01","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","pubrep_id":"752","oa_version":"Published Version","ddc":["571"],"page":"308 - 314","project":[{"_id":"25C26B1E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P24909-B24","name":"Mechanisms of transmitter release at GABAergic synapses"},{"name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","call_identifier":"FP7","_id":"25C0F108-B435-11E9-9278-68D0E5697425","grant_number":"268548"}],"department":[{"_id":"PeJo"},{"_id":"JoCs"}],"ec_funded":1,"type":"journal_article","scopus_import":"1","oa":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"},"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"ScienComp"},{"_id":"PreCl"}],"fulldoi":"https://doi.org/10.1016/j.neuron.2016.12.018","citation":{"short":"J. Gan, S.-M. Weng, A. Pernia-Andrade, J.L. Csicsvari, P.M. Jonas, Neuron 93 (2017) 308–314.","chicago":"Gan, Jian, Shih-Ming Weng, Alejandro Pernia-Andrade, Jozsef L Csicsvari, and Peter M Jonas. “Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice in Vivo.” <i>Neuron</i>. Elsevier, 2017. <a href=\"https://doi.org/10.1016/j.neuron.2016.12.018\">https://doi.org/10.1016/j.neuron.2016.12.018</a>.","ista":"Gan J, Weng S-M, Pernia-Andrade A, Csicsvari JL, Jonas PM. 2017. Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. Neuron. 93(2), 308–314.","ieee":"J. Gan, S.-M. Weng, A. Pernia-Andrade, J. L. Csicsvari, and P. M. Jonas, “Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo,” <i>Neuron</i>, vol. 93, no. 2. Elsevier, pp. 308–314, 2017.","mla":"Gan, Jian, et al. “Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice in Vivo.” <i>Neuron</i>, vol. 93, no. 2, Elsevier, 2017, pp. 308–14, doi:<a href=\"https://doi.org/10.1016/j.neuron.2016.12.018\">10.1016/j.neuron.2016.12.018</a>.","apa":"Gan, J., Weng, S.-M., Pernia-Andrade, A., Csicsvari, J. L., &#38; Jonas, P. M. (2017). Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2016.12.018\">https://doi.org/10.1016/j.neuron.2016.12.018</a>","ama":"Gan J, Weng S-M, Pernia-Andrade A, Csicsvari JL, Jonas PM. Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. <i>Neuron</i>. 2017;93(2):308-314. doi:<a href=\"https://doi.org/10.1016/j.neuron.2016.12.018\">10.1016/j.neuron.2016.12.018</a>"},"file":[{"access_level":"open_access","date_updated":"2018-12-12T10:08:56Z","relation":"main_file","date_created":"2018-12-12T10:08:56Z","file_id":"4719","file_size":2738950,"file_name":"IST-2017-752-v1+1_1-s2.0-S0896627316309606-main.pdf","creator":"system","content_type":"application/pdf"}],"file_date_updated":"2018-12-12T10:08:56Z","day":"18"},{"doi":"10.1016/j.devcel.2017.01.010","date_updated":"2025-07-10T11:49:55Z","date_created":"2018-12-11T11:49:58Z","ddc":["572","597"],"oa_version":"Published Version","pubrep_id":"869","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"02","project":[{"name":"Developing High-Throughput Bioassays for Human Cancers in Zebrafish","grant_number":"201439","_id":"2524F500-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"page":"354 - 366","type":"journal_article","ec_funded":1,"department":[{"_id":"CaHe"}],"scopus_import":"1","oa":1,"fulldoi":"https://doi.org/10.1016/j.devcel.2017.01.010","acknowledged_ssus":[{"_id":"PreCl"}],"citation":{"short":"H. Morita, S. Grigolon, M. Bock, G. Krens, G. Salbreux, C.-P.J. Heisenberg, Developmental Cell 40 (2017) 354–366.","chicago":"Morita, Hitoshi, Silvia Grigolon, Martin Bock, Gabriel Krens, Guillaume Salbreux, and Carl-Philipp J Heisenberg. “The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation.” <i>Developmental Cell</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.devcel.2017.01.010\">https://doi.org/10.1016/j.devcel.2017.01.010</a>.","ista":"Morita H, Grigolon S, Bock M, Krens G, Salbreux G, Heisenberg C-PJ. 2017. The physical basis of coordinated tissue spreading in zebrafish gastrulation. Developmental Cell. 40(4), 354–366.","mla":"Morita, Hitoshi, et al. “The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation.” <i>Developmental Cell</i>, vol. 40, no. 4, Cell Press, 2017, pp. 354–66, doi:<a href=\"https://doi.org/10.1016/j.devcel.2017.01.010\">10.1016/j.devcel.2017.01.010</a>.","ieee":"H. Morita, S. Grigolon, M. Bock, G. Krens, G. Salbreux, and C.-P. J. Heisenberg, “The physical basis of coordinated tissue spreading in zebrafish gastrulation,” <i>Developmental Cell</i>, vol. 40, no. 4. Cell Press, pp. 354–366, 2017.","apa":"Morita, H., Grigolon, S., Bock, M., Krens, G., Salbreux, G., &#38; Heisenberg, C.-P. J. (2017). The physical basis of coordinated tissue spreading in zebrafish gastrulation. <i>Developmental Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.devcel.2017.01.010\">https://doi.org/10.1016/j.devcel.2017.01.010</a>","ama":"Morita H, Grigolon S, Bock M, Krens G, Salbreux G, Heisenberg C-PJ. The physical basis of coordinated tissue spreading in zebrafish gastrulation. <i>Developmental Cell</i>. 2017;40(4):354-366. doi:<a href=\"https://doi.org/10.1016/j.devcel.2017.01.010\">10.1016/j.devcel.2017.01.010</a>"},"publication_identifier":{"issn":["1534-5807"]},"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"},"file_date_updated":"2018-12-12T10:10:57Z","file":[{"access_level":"open_access","creator":"system","content_type":"application/pdf","file_id":"4849","file_size":6866187,"file_name":"IST-2017-869-v1+1_1-s2.0-S1534580717300370-main.pdf","relation":"main_file","date_created":"2018-12-12T10:10:57Z","date_updated":"2018-12-12T10:10:57Z"}],"day":"27","isi":1,"publist_id":"6320","has_accepted_license":"1","year":"2017","publication_status":"published","date_published":"2017-02-27T00:00:00Z","title":"The physical basis of coordinated tissue spreading in zebrafish gastrulation","author":[{"full_name":"Morita, Hitoshi","id":"4C6E54C6-F248-11E8-B48F-1D18A9856A87","last_name":"Morita","first_name":"Hitoshi"},{"full_name":"Grigolon, Silvia","first_name":"Silvia","last_name":"Grigolon"},{"first_name":"Martin","last_name":"Bock","full_name":"Bock, Martin"},{"full_name":"Krens, Gabriel","id":"2B819732-F248-11E8-B48F-1D18A9856A87","last_name":"Krens","first_name":"Gabriel","orcid":"0000-0003-4761-5996"},{"full_name":"Salbreux, Guillaume","last_name":"Salbreux","first_name":"Guillaume"},{"last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"}],"publisher":"Cell Press","article_processing_charge":"No","_id":"1067","quality_controlled":"1","issue":"4","external_id":{"isi":["000395368300007"]},"abstract":[{"text":"Embryo morphogenesis relies on highly coordinated movements of different tissues. However, remarkably little is known about how tissues coordinate their movements to shape the embryo. In zebrafish embryogenesis, coordinated tissue movements first become apparent during “doming,” when the blastoderm begins to spread over the yolk sac, a process involving coordinated epithelial surface cell layer expansion and mesenchymal deep cell intercalations. Here, we find that active surface cell expansion represents the key process coordinating tissue movements during doming. By using a combination of theory and experiments, we show that epithelial surface cells not only trigger blastoderm expansion by reducing tissue surface tension, but also drive blastoderm thinning by inducing tissue contraction through radial deep cell intercalations. Thus, coordinated tissue expansion and thinning during doming relies on surface cells simultaneously controlling tissue surface tension and radial tissue contraction.","lang":"eng"}],"status":"public","language":[{"iso":"eng"}],"intvolume":"        40","volume":40,"publication":"Developmental Cell"},{"date_updated":"2026-04-16T09:57:27Z","date_created":"2018-12-11T11:49:20Z","doi":"10.1016/j.neuron.2017.04.012","oa_version":"None","corr_author":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"05","project":[{"call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"_id":"25D7962E-B435-11E9-9278-68D0E5697425","grant_number":"RGP0053/2014","name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level"}],"page":"517 - 533.e3","type":"journal_article","ec_funded":1,"department":[{"_id":"SiHi"},{"_id":"MaJö"}],"scopus_import":"1","fulldoi":"https://doi.org/10.1016/j.neuron.2017.04.012","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"citation":{"ieee":"R. J. Beattie <i>et al.</i>, “Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells,” <i>Neuron</i>, vol. 94, no. 3. Cell Press, p. 517–533.e3, 2017.","mla":"Beattie, Robert J., et al. “Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” <i>Neuron</i>, vol. 94, no. 3, Cell Press, 2017, p. 517–533.e3, doi:<a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">10.1016/j.neuron.2017.04.012</a>.","apa":"Beattie, R. J., Postiglione, M. P., Burnett, L., Laukoter, S., Streicher, C., Pauler, F., … Hippenmeyer, S. (2017). Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. <i>Neuron</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">https://doi.org/10.1016/j.neuron.2017.04.012</a>","ama":"Beattie RJ, Postiglione MP, Burnett L, et al. Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. <i>Neuron</i>. 2017;94(3):517-533.e3. doi:<a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">10.1016/j.neuron.2017.04.012</a>","chicago":"Beattie, Robert J, Maria P Postiglione, Laura Burnett, Susanne Laukoter, Carmen Streicher, Florian Pauler, Guanxi Xiao, et al. “Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” <i>Neuron</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">https://doi.org/10.1016/j.neuron.2017.04.012</a>.","ista":"Beattie RJ, Postiglione MP, Burnett L, Laukoter S, Streicher C, Pauler F, Xiao G, Klezovitch O, Vasioukhin V, Ghashghaei T, Hippenmeyer S. 2017. Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. Neuron. 94(3), 517–533.e3.","short":"R.J. Beattie, M.P. Postiglione, L. Burnett, S. Laukoter, C. Streicher, F. Pauler, G. Xiao, O. Klezovitch, V. Vasioukhin, T. Ghashghaei, S. Hippenmeyer, Neuron 94 (2017) 517–533.e3."},"publication_identifier":{"issn":["0896-6273"]},"day":"03","isi":1,"publist_id":"6473","year":"2017","publication_status":"published","date_published":"2017-05-03T00:00:00Z","author":[{"full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","last_name":"Beattie","orcid":"0000-0002-8483-8753","first_name":"Robert J"},{"first_name":"Maria P","last_name":"Postiglione","id":"2C67902A-F248-11E8-B48F-1D18A9856A87","full_name":"Postiglione, Maria P"},{"full_name":"Burnett, Laura","id":"3B717F68-F248-11E8-B48F-1D18A9856A87","last_name":"Burnett","orcid":"0000-0002-8937-410X","first_name":"Laura"},{"last_name":"Laukoter","first_name":"Susanne","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Streicher","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"orcid":"0000-0002-7462-0048","first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Xiao, Guanxi","first_name":"Guanxi","last_name":"Xiao"},{"full_name":"Klezovitch, Olga","last_name":"Klezovitch","first_name":"Olga"},{"first_name":"Valeri","last_name":"Vasioukhin","full_name":"Vasioukhin, Valeri"},{"full_name":"Ghashghaei, Troy","last_name":"Ghashghaei","first_name":"Troy"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"title":"Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells","publisher":"Cell Press","article_processing_charge":"No","_id":"944","quality_controlled":"1","issue":"3","external_id":{"isi":["000400466700011"]},"abstract":[{"text":"The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.","lang":"eng"}],"language":[{"iso":"eng"}],"intvolume":"        94","status":"public","volume":94,"publication":"Neuron"},{"year":"2017","has_accepted_license":"1","publication_status":"published","isi":1,"publist_id":"6907","title":"Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses","author":[{"full_name":"Chen, Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","first_name":"Chong","last_name":"Chen"},{"first_name":"Rachel","last_name":"Satterfield","full_name":"Satterfield, Rachel"},{"first_name":"Samuel","last_name":"Young","full_name":"Young, Samuel"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"date_published":"2017-11-21T00:00:00Z","quality_controlled":"1","external_id":{"isi":["000416216700007"]},"issue":"8","publisher":"Cell Press","article_processing_charge":"No","_id":"749","publication":"Cell Reports","volume":21,"language":[{"iso":"eng"}],"status":"public","intvolume":"        21","abstract":[{"text":"Synaptotagmin 7 (Syt7) is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, Syt7 is strongly expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. To resolve this apparent contradiction, we examined the effects of genetic elimination of Syt7 on synaptic transmission at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum. Our results indicate that at the BC-PC synapse, Syt7 contributes to asynchronous release, pool replenishment, and facilitation. In combination, these three effects ensure efficient transmitter release during high-frequency activity and guarantee frequency independence of inhibition. Our results identify a distinct function of Syt7: ensuring the efficiency of high-frequency inhibitory synaptic transmission","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","pubrep_id":"874","ddc":["570","571"],"oa_version":"Published Version","month":"11","date_created":"2018-12-11T11:48:18Z","date_updated":"2026-04-08T14:09:28Z","doi":"10.1016/j.celrep.2017.10.122","type":"journal_article","department":[{"_id":"PeJo"}],"ec_funded":1,"page":"2082 - 2089","project":[{"_id":"25C26B1E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P24909-B24","name":"Mechanisms of transmitter release at GABAergic synapses"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"}],"related_material":{"record":[{"id":"324","status":"public","relation":"dissertation_contains"}]},"fulldoi":"https://doi.org/10.1016/j.celrep.2017.10.122","citation":{"short":"C. Chen, R. Satterfield, S. Young, P.M. Jonas, Cell Reports 21 (2017) 2082–2089.","chicago":"Chen, Chong, Rachel Satterfield, Samuel Young, and Peter M Jonas. “Triple Function of Synaptotagmin 7 Ensures Efficiency of High-Frequency Transmission at Central GABAergic Synapses.” <i>Cell Reports</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.celrep.2017.10.122\">https://doi.org/10.1016/j.celrep.2017.10.122</a>.","ista":"Chen C, Satterfield R, Young S, Jonas PM. 2017. Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses. Cell Reports. 21(8), 2082–2089.","ieee":"C. Chen, R. Satterfield, S. Young, and P. M. Jonas, “Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses,” <i>Cell Reports</i>, vol. 21, no. 8. Cell Press, pp. 2082–2089, 2017.","apa":"Chen, C., Satterfield, R., Young, S., &#38; Jonas, P. M. (2017). Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2017.10.122\">https://doi.org/10.1016/j.celrep.2017.10.122</a>","mla":"Chen, Chong, et al. “Triple Function of Synaptotagmin 7 Ensures Efficiency of High-Frequency Transmission at Central GABAergic Synapses.” <i>Cell Reports</i>, vol. 21, no. 8, Cell Press, 2017, pp. 2082–89, doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.10.122\">10.1016/j.celrep.2017.10.122</a>.","ama":"Chen C, Satterfield R, Young S, Jonas PM. Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses. <i>Cell Reports</i>. 2017;21(8):2082-2089. doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.10.122\">10.1016/j.celrep.2017.10.122</a>"},"acknowledged_ssus":[{"_id":"PreCl"}],"publication_identifier":{"issn":["2211-1247"]},"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"},"oa":1,"scopus_import":"1","day":"21","file_date_updated":"2020-07-14T12:47:59Z","file":[{"checksum":"a6afa3764909bf6edafa07982d8e1cee","content_type":"application/pdf","creator":"system","relation":"main_file","date_updated":"2020-07-14T12:47:59Z","date_created":"2018-12-12T10:09:14Z","file_name":"IST-2017-874-v1+1_PIIS2211124717316029.pdf","file_size":2759195,"file_id":"4737","access_level":"open_access"}]},{"type":"journal_article","department":[{"_id":"PeJo"}],"ec_funded":1,"project":[{"name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","_id":"25C0F108-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"268548"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","oa_version":"Published Version","ddc":["571","572"],"pubrep_id":"715","month":"10","date_updated":"2025-09-22T08:26:29Z","date_created":"2018-12-11T11:51:22Z","doi":"10.7554/eLife.17977","day":"25","file_date_updated":"2020-07-14T12:44:44Z","file":[{"date_created":"2018-12-12T10:17:05Z","date_updated":"2020-07-14T12:44:44Z","relation":"main_file","file_name":"IST-2016-715-v1+1_e17977-download.pdf","file_size":1477891,"file_id":"5257","checksum":"a7201280c571bed88ebd459ce5ce6a47","content_type":"application/pdf","creator":"system","access_level":"open_access"}],"fulldoi":"https://doi.org/10.7554/eLife.17977","citation":{"ista":"Vyleta N, Borges Merjane C, Jonas PM. 2016. Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. eLife. 5, e17977.","chicago":"Vyleta, Nicholas, Carolina Borges Merjane, and Peter M Jonas. “Plasticity-Dependent, Full Detonation at Hippocampal Mossy Fiber–CA3 Pyramidal Neuron Synapses.” <i>ELife</i>. eLife Sciences Publications, 2016. <a href=\"https://doi.org/10.7554/eLife.17977\">https://doi.org/10.7554/eLife.17977</a>.","short":"N. Vyleta, C. Borges Merjane, P.M. Jonas, ELife 5 (2016).","ama":"Vyleta N, Borges Merjane C, Jonas PM. Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. <i>eLife</i>. 2016;5. doi:<a href=\"https://doi.org/10.7554/eLife.17977\">10.7554/eLife.17977</a>","mla":"Vyleta, Nicholas, et al. “Plasticity-Dependent, Full Detonation at Hippocampal Mossy Fiber–CA3 Pyramidal Neuron Synapses.” <i>ELife</i>, vol. 5, e17977, eLife Sciences Publications, 2016, doi:<a href=\"https://doi.org/10.7554/eLife.17977\">10.7554/eLife.17977</a>.","ieee":"N. Vyleta, C. Borges Merjane, and P. M. Jonas, “Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses,” <i>eLife</i>, vol. 5. eLife Sciences Publications, 2016.","apa":"Vyleta, N., Borges Merjane, C., &#38; Jonas, P. M. (2016). Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.17977\">https://doi.org/10.7554/eLife.17977</a>"},"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"}],"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"},"oa":1,"scopus_import":"1","title":"Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses","author":[{"full_name":"Vyleta, Nicholas","id":"36C4978E-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas","last_name":"Vyleta"},{"first_name":"Carolina","orcid":"0000-0003-0005-401X","last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87","full_name":"Borges Merjane, Carolina"},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804"}],"date_published":"2016-10-25T00:00:00Z","year":"2016","has_accepted_license":"1","publication_status":"published","isi":1,"publist_id":"5947","publication":"eLife","volume":5,"intvolume":"         5","language":[{"iso":"eng"}],"status":"public","abstract":[{"text":"Mossy fiber synapses on CA3 pyramidal cells are 'conditional detonators' that reliably discharge postsynaptic targets. The 'conditional' nature implies that burst activity in dentate gyrus granule cells is required for detonation. Whether single unitary excitatory postsynaptic potentials (EPSPs) trigger spikes in CA3 neurons remains unknown. Mossy fiber synapses exhibit both pronounced short-term facilitation and uniquely large post-tetanic potentiation (PTP). We tested whether PTP could convert mossy fiber synapses from subdetonator into detonator mode, using a recently developed method to selectively and noninvasively stimulate individual presynaptic terminals in rat brain slices. Unitary EPSPs failed to initiate a spike in CA3 neurons under control conditions, but reliably discharged them after induction of presynaptic short-term plasticity. Remarkably, PTP switched mossy fiber synapses into full detonators for tens of seconds. Plasticity-dependent detonation may be critical for efficient coding, storage, and recall of information in the granule cell–CA3 cell network.","lang":"eng"}],"quality_controlled":"1","external_id":{"isi":["000387034600001"]},"article_number":"e17977","publisher":"eLife Sciences Publications","article_processing_charge":"No","_id":"1323"},{"date_created":"2018-12-11T11:50:18Z","date_updated":"2026-07-29T11:30:22Z","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","corr_author":"1","ddc":["570"],"oa_version":"Published Version","month":"07","page":"178","type":"dissertation","department":[{"_id":"MiSi"},{"_id":"GradSch"}],"OA_place":"publisher","oa":1,"supervisor":[{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","orcid":"0000-0002-6620-9179","first_name":"Michael K"}],"citation":{"chicago":"Schwarz, Jan. “Quantitative Analysis of Haptotactic Cell Migration.” Institute of Science and Technology Austria, 2016.","ista":"Schwarz J. 2016. Quantitative analysis of haptotactic cell migration. Institute of Science and Technology Austria.","short":"J. Schwarz, Quantitative Analysis of Haptotactic Cell Migration, Institute of Science and Technology Austria, 2016.","mla":"Schwarz, Jan. <i>Quantitative Analysis of Haptotactic Cell Migration</i>. Institute of Science and Technology Austria, 2016.","apa":"Schwarz, J. (2016). <i>Quantitative analysis of haptotactic cell migration</i>. Institute of Science and Technology Austria.","ieee":"J. Schwarz, “Quantitative analysis of haptotactic cell migration,” Institute of Science and Technology Austria, 2016.","ama":"Schwarz J. Quantitative analysis of haptotactic cell migration. 2016."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"publication_identifier":{"issn":["2663-337X"]},"file_date_updated":"2021-02-22T11:43:14Z","doi_confirm":"1","file":[{"access_level":"closed","date_created":"2019-08-13T10:55:35Z","date_updated":"2019-08-13T10:55:35Z","relation":"main_file","file_size":32044069,"file_name":"Thesis_JSchwarz_final.pdf","file_id":"6813","checksum":"e3cd6b28f9c5cccb8891855565a2dade","content_type":"application/pdf","creator":"dernst"},{"content_type":"application/pdf","creator":"dernst","checksum":"c3dbe219acf87eed2f46d21d5cca00de","file_size":8396717,"file_name":"2016_Thesis_JSchwarz.pdf","file_id":"9181","date_created":"2021-02-22T11:43:14Z","date_updated":"2021-02-22T11:43:14Z","relation":"main_file","access_level":"open_access","success":1}],"day":"01","publist_id":"6231","year":"2016","has_accepted_license":"1","publication_status":"published","date_published":"2016-07-01T00:00:00Z","title":"Quantitative analysis of haptotactic cell migration","author":[{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","first_name":"Jan","last_name":"Schwarz"}],"publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","_id":"1129","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","language":[{"iso":"eng"}],"acknowledgement":"First, I would like to thank Michael Sixt for being a great supervisor, mentor and\r\nscientist. I highly appreciate his guidance and continued support. Furthermore, I\r\nam very grateful that he gave me the exceptional opportunity to pursue many\r\nideas of which some managed to be included in this thesis.\r\nI owe sincere thanks to the members of my PhD thesis committee, Daria\r\nSiekhaus, Daniel Legler and Harald Janovjak. Especially I would like to thank\r\nDaria for her advice and encouragement during our regular progress meetings.\r\nI also want to thank the team and fellows of the Boehringer Ingelheim Fond\r\n(BIF) PhD Fellowship for amazing and inspiring meetings and the BIF for\r\nfinancial support.\r\nImportant factors for the success of this thesis were the warm, creative\r\nand helpful atmosphere as well as the team spirit of the whole Sixt Lab.\r\nTherefore I would like to thank my current and former colleagues Frank Assen,\r\nMarkus Brown, Ingrid de Vries, Michelle Duggan, Alexander Eichner, Miroslav\r\nHons, Eva Kiermaier, Aglaja Kopf, Alexander Leithner, Christine Moussion, Jan\r\nMüller, Maria Nemethova, Jörg Renkawitz, Anne Reversat, Kari Vaahtomeri,\r\nMichele Weber and Stefan Wieser. We had an amazing time with many\r\nlegendary evenings and events. Along these lines I want to thank the in vitro\r\ncrew of the lab, Jörg, Anne and Alex, for lots of ideas and productive\r\ndiscussions. I am sure, some day we will reveal the secret of the ‘splodge’.\r\nI want to thank the members of the Heisenberg Lab for a great time and\r\nthrilling kicker matches. In this regard I especially want to thank Maurizio\r\n‘Gnocci’ Monti, Gabriel Krens, Alex Eichner, Martin Behrndt, Vanessa Barone,Philipp Schmalhorst, Michael Smutny, Daniel Capek, Anne Reversat, Eva\r\nKiermaier, Frank Assen and Jan Müller for wonderful after-lunch matches.\r\nI would not have been able to analyze the thousands of cell trajectories\r\nand probably hundreds of thousands of mouse clicks without the productive\r\ncollaboration with Veronika Bierbaum and Tobias Bollenbach. Thanks Vroni for\r\ncountless meetings, discussions and graphs and of course for proofreading and\r\nadvice for this thesis. For proofreading I also want to thank Evi, Jörg, Jack and\r\nAnne.\r\nI would like to acknowledge Matthias Mehling for a very productive\r\ncollaboration and for introducing me into the wild world of microfluidics. Jack\r\nMerrin, for countless wafers, PDMS coated coverslips and help with anything\r\nmicro-fabrication related. And Maria Nemethova for establishing the ‘click’\r\npatterning approach with me. Without her it still would be just one of the ideas…\r\nMany thanks to Ekaterina Papusheva, Robert Hauschild, Doreen Milius\r\nand Nasser Darwish from the Bioimaging Facility as well as the Preclinical and\r\nthe Life Science facilities of IST Austria for excellent technical support. At this\r\npoint I especially want to thank Robert for countless image analyses and\r\ntechnical ideas. Always interested and creative he played an essential role in all\r\nof my projects.\r\nAdditionally I want to thank Ingrid and Gabby for welcoming me warmly\r\nwhen I first started at IST, for scientific and especially mental support in all\r\nthose years, countless coffee sessions and Heurigen evenings. #BioimagingFacility #LifeScienceFacility #PreClinicalFacility","status":"public","abstract":[{"lang":"eng","text":"Directed cell migration is a hallmark feature, present in almost all multi-cellular\r\norganisms. Despite its importance, basic questions regarding force transduction\r\nor directional sensing are still heavily investigated. Directed migration of cells\r\nguided by immobilized guidance cues - haptotaxis - occurs in key-processes,\r\nsuch as embryonic development and immunity (Middleton et al., 1997; Nguyen\r\net al., 2000; Thiery, 1984; Weber et al., 2013). Immobilized guidance cues\r\ncomprise adhesive ligands, such as collagen and fibronectin (Barczyk et al.,\r\n2009), or chemokines - the main guidance cues for migratory leukocytes\r\n(Middleton et al., 1997; Weber et al., 2013). While adhesive ligands serve as\r\nattachment sites guiding cell migration (Carter, 1965), chemokines instruct\r\nhaptotactic migration by inducing adhesion to adhesive ligands and directional\r\nguidance (Rot and Andrian, 2004; Schumann et al., 2010). Quantitative analysis\r\nof the cellular response to immobilized guidance cues requires in vitro assays\r\nthat foster cell migration, offer accurate control of the immobilized cues on a\r\nsubcellular scale and in the ideal case closely reproduce in vivo conditions. The\r\nexploration of haptotactic cell migration through design and employment of such\r\nassays represents the main focus of this work.\r\nDendritic cells (DCs) are leukocytes, which after encountering danger\r\nsignals such as pathogens in peripheral organs instruct naïve T-cells and\r\nconsequently the adaptive immune response in the lymph node (Mellman and\r\nSteinman, 2001). To reach the lymph node from the periphery, DCs follow\r\nhaptotactic gradients of the chemokine CCL21 towards lymphatic vessels\r\n(Weber et al., 2013). Questions about how DCs interpret haptotactic CCL21\r\ngradients have not yet been addressed. The main reason for this is the lack of\r\nan assay that offers diverse haptotactic environments, hence allowing the study\r\nof DC migration as a response to different signals of immobilized guidance cue.\r\nIn this work, we developed an in vitro assay that enables us to\r\nquantitatively assess DC haptotaxis, by combining precisely controllable\r\nchemokine photo-patterning with physically confining migration conditions. With this tool at hand, we studied the influence of CCL21 gradient properties and\r\nconcentration on DC haptotaxis. We found that haptotactic gradient sensing\r\ndepends on the absolute CCL21 concentration in combination with the local\r\nsteepness of the gradient. Our analysis suggests that the directionality of\r\nmigrating DCs is governed by the signal-to-noise ratio of CCL21 binding to its\r\nreceptor CCR7. Moreover, the haptotactic CCL21 gradient formed in vivo\r\nprovides an optimal shape for DCs to recognize haptotactic guidance cue.\r\nBy reconstitution of the CCL21 gradient in vitro we were also able to\r\nstudy the influence of CCR7 signal termination on DC haptotaxis. To this end,\r\nwe used DCs lacking the G-protein coupled receptor kinase GRK6, which is\r\nresponsible for CCL21 induced CCR7 receptor phosphorylation and\r\ndesensitization (Zidar et al., 2009). We found that CCR7 desensitization by\r\nGRK6 is crucial for maintenance of haptotactic CCL21 gradient sensing in vitro\r\nand confirm those observations in vivo.\r\nIn the context of the organism, immobilized haptotactic guidance cues\r\noften coincide and compete with soluble chemotactic guidance cues. During\r\nwound healing, fibroblasts are exposed and influenced by adhesive cues and\r\nsoluble factors at the same time (Wu et al., 2012; Wynn, 2008). Similarly,\r\nmigrating DCs are exposed to both, soluble chemokines (CCL19 and truncated\r\nCCL21) inducing chemotactic behavior as well as the immobilized CCL21. To\r\nquantitatively assess these complex coinciding immobilized and soluble\r\nguidance cues, we implemented our chemokine photo-patterning technique in a\r\nmicrofluidic system allowing for chemotactic gradient generation. To validate\r\nthe assay, we observed DC migration in competing CCL19/CCL21\r\nenvironments.\r\nAdhesiveness guided haptotaxis has been studied intensively over the\r\nlast century. However, quantitative studies leading to conceptual models are\r\nlargely missing, again due to the lack of a precisely controllable in vitro assay. A\r\nrequirement for such an in vitro assay is that it must prevent any uncontrolled\r\ncell adhesion. This can be accomplished by stable passivation of the surface. In\r\naddition, controlled adhesion must be sustainable, quantifiable and dose\r\ndependent in order to create homogenous gradients. Therefore, we developed a novel covalent photo-patterning technique satisfying all these needs. In\r\ncombination with a sustainable poly-vinyl alcohol (PVA) surface coating we\r\nwere able to generate gradients of adhesive cue to direct cell migration. This\r\napproach allowed us to characterize the haptotactic migratory behavior of\r\nzebrafish keratocytes in vitro. Furthermore, defined patterns of adhesive cue\r\nallowed us to control for cell shape and growth on a subcellular scale."}]},{"day":"01","doi_confirm":"1","abstract":[{"lang":"eng","text":"Epithelial spreading is a critical part of various developmental and wound repair processes. Here we use zebrafish epiboly as a model system to study the cellular and molecular mechanisms underlying the spreading of epithelial sheets. During zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the embryo to eventually cover the entire yolk cell by the end of gastrulation. The EVL leading edge is anchored through tight junctions to the yolk syncytial layer (YSL), where directly adjacent to the EVL margin a contractile actomyosin ring is formed that is thought to drive EVL epiboly. The prevalent view in the field was that the contractile ring exerts a pulling force on the EVL margin, which pulls the EVL towards the vegetal pole. However, how this force is generated and how it affects EVL morphology still remains elusive. Moreover, the cellular mechanisms mediating the increase in EVL surface area, while maintaining tissue integrity and function are still unclear. Here we show that the YSL actomyosin ring pulls on the EVL margin by two distinct force-generating mechanisms. One mechanism is based on contraction of the ring around its circumference, as previously proposed. The second mechanism is based on actomyosin retrogade flows, generating force through resistance against the substrate. The latter can function at any epiboly stage even in situations where the contraction-based mechanism is unproductive. Additionally, we demonstrate that during epiboly the EVL is subjected to anisotropic tension, which guides the orientation of EVL cell division along the main axis (animal-vegetal) of tension. The influence of tension in cell division orientation involves cell elongation and requires myosin-2 activity for proper spindle alignment. Strikingly, we reveal that tension-oriented cell divisions release anisotropic tension within the EVL and that in the absence of such divisions, EVL cells undergo ectopic fusions. We conclude that forces applied to the EVL by the action of the YSL actomyosin ring generate a tension anisotropy in the EVL that orients cell divisions, which in turn limit tissue tension increase thereby facilitating tissue spreading."}],"status":"public","language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","last_name":"Heisenberg"}],"citation":{"short":"P. Campinho, Mechanics of Zebrafish Epiboly: Tension-Oriented Cell Divisions Limit Anisotropic Tissue Tension in Epithelial Spreading, Institute of Science and Technology Austria, 2013.","chicago":"Campinho, Pedro. “Mechanics of Zebrafish Epiboly: Tension-Oriented Cell Divisions Limit Anisotropic Tissue Tension in Epithelial Spreading.” Institute of Science and Technology Austria, 2013.","ista":"Campinho P. 2013. Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading. Institute of Science and Technology Austria.","apa":"Campinho, P. (2013). <i>Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading</i>. Institute of Science and Technology Austria.","mla":"Campinho, Pedro. <i>Mechanics of Zebrafish Epiboly: Tension-Oriented Cell Divisions Limit Anisotropic Tissue Tension in Epithelial Spreading</i>. Institute of Science and Technology Austria, 2013.","ieee":"P. Campinho, “Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading,” Institute of Science and Technology Austria, 2013.","ama":"Campinho P. Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading. 2013."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"publication_identifier":{"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"],"_id":"1406","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","OA_place":"publisher","title":"Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading","department":[{"_id":"CaHe"},{"_id":"GradSch"}],"author":[{"last_name":"Campinho","first_name":"Pedro","orcid":"0000-0002-8526-5416","id":"3AFBBC42-F248-11E8-B48F-1D18A9856A87","full_name":"Campinho, Pedro"}],"type":"dissertation","date_published":"2013-10-01T00:00:00Z","page":"123","month":"10","publication_status":"published","oa_version":"None","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","year":"2013","corr_author":"1","publist_id":"5801","date_created":"2018-12-11T11:51:50Z","date_updated":"2026-07-29T10:00:09Z"},{"year":"2013","publication_status":"published","isi":1,"publist_id":"4652","title":"Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly","author":[{"full_name":"Campinho, Pedro","id":"3AFBBC42-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8526-5416","first_name":"Pedro","last_name":"Campinho"},{"id":"3ECECA3A-F248-11E8-B48F-1D18A9856A87","full_name":"Behrndt, Martin","last_name":"Behrndt","first_name":"Martin"},{"first_name":"Jonas","last_name":"Ranft","full_name":"Ranft, Jonas"},{"last_name":"Risler","first_name":"Thomas","full_name":"Risler, Thomas"},{"full_name":"Minc, Nicolas","last_name":"Minc","first_name":"Nicolas"},{"last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"}],"date_published":"2013-11-10T00:00:00Z","quality_controlled":"1","external_id":{"isi":["000327944200005"]},"publisher":"Nature Publishing Group","article_processing_charge":"No","_id":"2282","publication":"Nature Cell Biology","volume":15,"language":[{"iso":"eng"}],"status":"public","intvolume":"        15","acknowledgement":"This work was supported by the IST Austria and MPI-CBG ","abstract":[{"text":"Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.","lang":"eng"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","oa_version":"Submitted Version","month":"11","date_created":"2018-12-11T11:56:45Z","date_updated":"2026-07-29T10:07:18Z","doi":"10.1038/ncb2869","type":"journal_article","department":[{"_id":"CaHe"}],"page":"1405 - 1414","project":[{"grant_number":"I930-B20","call_identifier":"FWF","_id":"252ABD0A-B435-11E9-9278-68D0E5697425","name":"Control of Epithelial Cell Layer Spreading in Zebrafish"}],"related_material":{"record":[{"id":"1403","relation":"dissertation_contains","status":"public"}]},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"fulldoi":"https://doi.org/10.1038/ncb2869","citation":{"chicago":"Campinho, Pedro, Martin Behrndt, Jonas Ranft, Thomas Risler, Nicolas Minc, and Carl-Philipp J Heisenberg. “Tension-Oriented Cell Divisions Limit Anisotropic Tissue Tension in Epithelial Spreading during Zebrafish Epiboly.” <i>Nature Cell Biology</i>. Nature Publishing Group, 2013. <a href=\"https://doi.org/10.1038/ncb2869\">https://doi.org/10.1038/ncb2869</a>.","ista":"Campinho P, Behrndt M, Ranft J, Risler T, Minc N, Heisenberg C-PJ. 2013. Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly. Nature Cell Biology. 15, 1405–1414.","short":"P. Campinho, M. Behrndt, J. Ranft, T. Risler, N. Minc, C.-P.J. Heisenberg, Nature Cell Biology 15 (2013) 1405–1414.","ieee":"P. Campinho, M. Behrndt, J. Ranft, T. Risler, N. Minc, and C.-P. J. Heisenberg, “Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly,” <i>Nature Cell Biology</i>, vol. 15. Nature Publishing Group, pp. 1405–1414, 2013.","apa":"Campinho, P., Behrndt, M., Ranft, J., Risler, T., Minc, N., &#38; Heisenberg, C.-P. J. (2013). Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly. <i>Nature Cell Biology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ncb2869\">https://doi.org/10.1038/ncb2869</a>","mla":"Campinho, Pedro, et al. “Tension-Oriented Cell Divisions Limit Anisotropic Tissue Tension in Epithelial Spreading during Zebrafish Epiboly.” <i>Nature Cell Biology</i>, vol. 15, Nature Publishing Group, 2013, pp. 1405–14, doi:<a href=\"https://doi.org/10.1038/ncb2869\">10.1038/ncb2869</a>.","ama":"Campinho P, Behrndt M, Ranft J, Risler T, Minc N, Heisenberg C-PJ. Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly. <i>Nature Cell Biology</i>. 2013;15:1405-1414. doi:<a href=\"https://doi.org/10.1038/ncb2869\">10.1038/ncb2869</a>"},"scopus_import":"1","oa":1,"main_file_link":[{"url":"http://hal.upmc.fr/hal-00983313/","open_access":"1"}],"day":"10"},{"date_created":"2018-12-11T12:03:06Z","date_updated":"2026-07-28T08:23:30Z","doi":"10.1242/dev.071233","ddc":["570"],"oa_version":"Published Version","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"11","page":"4673 - 4683","type":"journal_article","department":[{"_id":"CaHe"}],"scopus_import":"1","oa":1,"fulldoi":"https://doi.org/10.1242/dev.071233","citation":{"mla":"Stockinger, Petra, et al. “Defective Neuroepithelial Cell Cohesion Affects Tangential Branchiomotor Neuron Migration in the Zebrafish Neural Tube.” <i>Development</i>, vol. 138, no. 21, Company of Biologists, 2011, pp. 4673–83, doi:<a href=\"https://doi.org/10.1242/dev.071233\">10.1242/dev.071233</a>.","apa":"Stockinger, P., Heisenberg, C.-P. J., &#38; Maître, J.-L. (2011). Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube. <i>Development</i>. Company of Biologists. <a href=\"https://doi.org/10.1242/dev.071233\">https://doi.org/10.1242/dev.071233</a>","ieee":"P. Stockinger, C.-P. J. Heisenberg, and J.-L. Maître, “Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube,” <i>Development</i>, vol. 138, no. 21. Company of Biologists, pp. 4673–4683, 2011.","ama":"Stockinger P, Heisenberg C-PJ, Maître J-L. Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube. <i>Development</i>. 2011;138(21):4673-4683. doi:<a href=\"https://doi.org/10.1242/dev.071233\">10.1242/dev.071233</a>","short":"P. Stockinger, C.-P.J. Heisenberg, J.-L. Maître, Development 138 (2011) 4673–4683.","chicago":"Stockinger, Petra, Carl-Philipp J Heisenberg, and Jean-Léon Maître. “Defective Neuroepithelial Cell Cohesion Affects Tangential Branchiomotor Neuron Migration in the Zebrafish Neural Tube.” <i>Development</i>. Company of Biologists, 2011. <a href=\"https://doi.org/10.1242/dev.071233\">https://doi.org/10.1242/dev.071233</a>.","ista":"Stockinger P, Heisenberg C-PJ, Maître J-L. 2011. Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube. Development. 138(21), 4673–4683."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"file_date_updated":"2020-07-14T12:46:12Z","file":[{"date_updated":"2020-07-14T12:46:12Z","date_created":"2019-10-07T14:19:42Z","relation":"main_file","file_size":4672439,"file_name":"2011_Development_Stockinger.pdf","file_id":"6930","checksum":"ca12b79e01ef36c1ef1aea31cf7e7139","content_type":"application/pdf","creator":"dernst","access_level":"open_access"}],"day":"01","article_type":"original","isi":1,"publist_id":"3210","has_accepted_license":"1","year":"2011","publication_status":"published","date_published":"2011-11-01T00:00:00Z","author":[{"full_name":"Stockinger, Petra","id":"261CB030-E90D-11E9-B182-F697D44B663C","last_name":"Stockinger","first_name":"Petra"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"},{"full_name":"Maître, Jean-Léon","id":"48F1E0D8-F248-11E8-B48F-1D18A9856A87","last_name":"Maître","orcid":"0000-0002-3688-1474","first_name":"Jean-Léon"}],"title":"Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube","publisher":"Company of Biologists","article_processing_charge":"No","_id":"3396","quality_controlled":"1","keyword":["Epithelial cohesion","Hindbrain","Neuronal migration","Zebrafish"],"issue":"21","external_id":{"isi":["000296060100011"]},"abstract":[{"lang":"eng","text":"Facial branchiomotor neurons (FBMNs) in zebrafish and mouse embryonic hindbrain undergo a characteristic tangential migration from rhombomere (r) 4, where they are born, to r6/7. Cohesion among neuroepithelial cells (NCs) has been suggested to function in FBMN migration by inhibiting FBMNs positioned in the basal neuroepithelium such that they move apically between NCs towards the midline of the neuroepithelium instead of tangentially along the basal side of the neuroepithelium towards r6/7. However, direct experimental evaluation of this hypothesis is still lacking. Here, we have used a combination of biophysical cell adhesion measurements and high-resolution time-lapse microscopy to determine the role of NC cohesion in FBMN migration. We show that reducing NC cohesion by interfering with Cadherin 2 (Cdh2) activity results in FBMNs positioned at the basal side of the neuroepithelium moving apically towards the neural tube midline instead of tangentially towards r6/7. In embryos with strongly reduced NC cohesion, ectopic apical FBMN movement frequently results in fusion of the bilateral FBMN clusters over the apical midline of the neural tube. By contrast, reducing cohesion among FBMNs by interfering with Contactin 2 (Cntn2) expression in these cells has little effect on apical FBMN movement, but reduces the fusion of the bilateral FBMN clusters in embryos with strongly diminished NC cohesion. These data provide direct experimental evidence that NC cohesion functions in tangential FBMN migration by restricting their apical movement."}],"intvolume":"       138","acknowledgement":"We thank C. Moens and J. Geiger for critical reading of earlier versions of this manuscript and members of the Heisenberg laboratory for discussions. We are grateful to the microscopy facility of the MPI-CBG and IST Austria for continuous support; I. Nüsslein, J. Compagnon and Alex Eichner for help with cell sorting; and the fish facility of the MPI-CBG and IST Austria for excellent fish care.","status":"public","language":[{"iso":"eng"}],"volume":138,"publication":"Development"}]