[{"article_type":"original","day":"06","file":[{"content_type":"application/pdf","creator":"cziletti","checksum":"f056255f6d01fd9a86b5387635928173","file_name":"2021_CellReports_Venturino.pdf","file_size":56388540,"file_id":"9693","date_updated":"2021-07-19T13:32:17Z","relation":"main_file","date_created":"2021-07-19T13:32:17Z","access_level":"open_access","success":1}],"file_date_updated":"2021-07-19T13:32:17Z","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":{"eissn":["2211-1247"]},"fulldoi":"https://doi.org/10.1016/j.celrep.2021.109313","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"citation":{"apa":"Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar, F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">https://doi.org/10.1016/j.celrep.2021.109313</a>","ieee":"A. Venturino <i>et al.</i>, “Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,” <i>Cell Reports</i>, vol. 36, no. 1. Elsevier, 2021.","mla":"Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>, vol. 36, no. 1, 109313, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">10.1016/j.celrep.2021.109313</a>.","ama":"Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. 2021;36(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">10.1016/j.celrep.2021.109313</a>","short":"A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar, G. Colombo, R.J. Cubero, F.E. Miteva, M.F. Bear, S. Siegert, Cell Reports 36 (2021).","chicago":"Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">https://doi.org/10.1016/j.celrep.2021.109313</a>.","ista":"Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar F, Colombo G, Cubero RJ, Miteva FE, Bear MF, Siegert S. 2021. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313."},"oa":1,"scopus_import":"1","ec_funded":1,"department":[{"_id":"SaSi"}],"type":"journal_article","related_material":{"link":[{"url":"https://ist.ac.at/en/news/the-twinkle-and-the-brain/","relation":"press_release","description":"News on IST Homepage"}]},"pmid":1,"project":[{"grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"name":"Microglia action towards neuronal circuit formation and function in health and disease","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571"}],"month":"07","ddc":["570"],"oa_version":"Published Version","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","doi":"10.1016/j.celrep.2021.109313","date_created":"2021-07-11T22:01:16Z","date_updated":"2026-04-03T09:46:05Z","volume":36,"publication":"Cell Reports","abstract":[{"text":"Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain.","lang":"eng"}],"language":[{"iso":"eng"}],"license":"https://creativecommons.org/licenses/by/4.0/","acknowledgement":"We thank the scientific service units at IST Austria, especially the IST bioimaging facility, the preclinical facility, and, specifically, Michael Schunn and Sonja Haslinger for excellent support; Plexxikon for the PLX food; the Csicsvari group for advice and equipment for in vivo recording; Jürgen Siegert for the light-entrainment design; Marco Benevento, Soledad Gonzalo Cogno, Pat King, and all Siegert group members for constant feedback on the project and manuscript; Lorena Pantano (PILM Bioinformatics Core) for assisting with sample-size determination for OD plasticity experiments; and Ana Morello from MIT for technical assistance with VEPs recordings. This research was supported by a DOC Fellowship from the Austrian Academy of Sciences at the Institute of Science and Technology Austria to R.S., from the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (grants 665385 to G.C.; 754411 to R.J.A.C.), the European Research Council (grant 715571 to S.S.), and the National Eye Institute of the National Institutes of Health under award numbers R01EY029245 (to M.F.B.) and R01EY023037 (diversity supplement to H.D.J-C.).","status":"public","intvolume":"        36","article_number":"109313","issue":"1","external_id":{"isi":["000670188500004"],"pmid":["34233180"]},"quality_controlled":"1","_id":"9642","publisher":"Elsevier","article_processing_charge":"No","author":[{"full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","orcid":"0000-0003-2356-9403","first_name":"Alessandro"},{"orcid":"0000-0001-5297-733X","first_name":"Rouven","last_name":"Schulz","full_name":"Schulz, Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"},{"full_name":"De Jesús-Cortés, Héctor","first_name":"Héctor","last_name":"De Jesús-Cortés"},{"id":"3838F452-F248-11E8-B48F-1D18A9856A87","full_name":"Maes, Margaret E","last_name":"Maes","orcid":"0000-0001-9642-1085","first_name":"Margaret E"},{"last_name":"Nagy","first_name":"Balint","full_name":"Nagy, Balint","id":"93C65ECC-A6F2-11E9-8DF9-9712E6697425"},{"full_name":"Reilly-Andújar, Francis","first_name":"Francis","last_name":"Reilly-Andújar"},{"full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","orcid":"0000-0001-9434-8902","last_name":"Colombo"},{"full_name":"Cubero, Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425","first_name":"Ryan J","orcid":"0000-0003-0002-1867","last_name":"Cubero"},{"last_name":"Schoot Uiterkamp","first_name":"Florianne E","full_name":"Schoot Uiterkamp, Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bear, Mark F.","last_name":"Bear","first_name":"Mark F."},{"last_name":"Siegert","orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra"}],"title":"Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain","date_published":"2021-07-06T00:00:00Z","publication_status":"published","has_accepted_license":"1","year":"2021","isi":1},{"day":"20","scopus_import":"1","editor":[{"full_name":"Dosch, Roland","first_name":"Roland","last_name":"Dosch"}],"fulldoi":"https://doi.org/10.1007/978-1-0716-0970-5_10","publication_identifier":{"eissn":["1940-6029"],"eisbn":["978-1-0716-0970-5"],"isbn":["978-1-0716-0969-9"],"issn":["1064-3745"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"citation":{"ista":"Xia P, Heisenberg C-PJ. 2021.Quantifying tissue tension in the granulosa layer after laser surgery. In: Germline Development in the Zebrafish. Methods in Molecular Biology, vol. 2218, 117–128.","chicago":"Xia, Peng, and Carl-Philipp J Heisenberg. “Quantifying Tissue Tension in the Granulosa Layer after Laser Surgery.” In <i>Germline Development in the Zebrafish</i>, edited by Roland Dosch, 2218:117–28. Humana Press, 2021. <a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">https://doi.org/10.1007/978-1-0716-0970-5_10</a>.","short":"P. Xia, C.-P.J. Heisenberg, in:, R. Dosch (Ed.), Germline Development in the Zebrafish, Humana Press, 2021, pp. 117–128.","ama":"Xia P, Heisenberg C-PJ. Quantifying tissue tension in the granulosa layer after laser surgery. In: Dosch R, ed. <i>Germline Development in the Zebrafish</i>. Vol 2218. Humana Press; 2021:117-128. doi:<a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">10.1007/978-1-0716-0970-5_10</a>","apa":"Xia, P., &#38; Heisenberg, C.-P. J. (2021). Quantifying tissue tension in the granulosa layer after laser surgery. In R. Dosch (Ed.), <i>Germline Development in the Zebrafish</i> (Vol. 2218, pp. 117–128). Humana Press. <a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">https://doi.org/10.1007/978-1-0716-0970-5_10</a>","mla":"Xia, Peng, and Carl-Philipp J. Heisenberg. “Quantifying Tissue Tension in the Granulosa Layer after Laser Surgery.” <i>Germline Development in the Zebrafish</i>, edited by Roland Dosch, vol. 2218, Humana Press, 2021, pp. 117–28, doi:<a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">10.1007/978-1-0716-0970-5_10</a>.","ieee":"P. Xia and C.-P. J. Heisenberg, “Quantifying tissue tension in the granulosa layer after laser surgery,” in <i>Germline Development in the Zebrafish</i>, vol. 2218, R. Dosch, Ed. Humana Press, 2021, pp. 117–128."},"pmid":1,"project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"page":"117-128","ec_funded":1,"department":[{"_id":"CaHe"}],"type":"book_chapter","date_created":"2021-03-14T23:01:34Z","date_updated":"2026-07-06T13:11:10Z","doi":"10.1007/978-1-0716-0970-5_10","month":"02","oa_version":"None","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","abstract":[{"lang":"eng","text":"Tissue morphogenesis is driven by mechanical forces triggering cell movements and shape changes. Quantitatively measuring tension within tissues is of great importance for understanding the role of mechanical signals acting on the cell and tissue level during morphogenesis. Here we introduce laser ablation as a useful tool to probe tissue tension within the granulosa layer, an epithelial monolayer of somatic cells that surround the zebrafish female gamete during folliculogenesis. We describe in detail how to isolate follicles, mount samples, perform laser surgery, and analyze the data."}],"intvolume":"      2218","status":"public","acknowledgement":"We thank Prof. Masazumi Tada and Roland Dosch for providing transgenic zebrafish lines, the Heisenberg lab for technical assistance and feedback on the manuscript, and the Bioimaging and Fish facilities of IST Austria for continuous support. This work was funded by an ERC advanced grant (MECSPEC to C.-P.H.).","language":[{"iso":"eng"}],"volume":2218,"publication":"Germline Development in the Zebrafish","_id":"9245","article_processing_charge":"No","publisher":"Humana Press","external_id":{"pmid":["33606227"]},"alternative_title":["Methods in Molecular Biology"],"quality_controlled":"1","keyword":["Tissue tension","Morphogenesis","Laser ablation","Zebrafish folliculogenesis","Granulosa cells"],"das_tickbox":"1","date_published":"2021-02-20T00:00:00Z","title":"Quantifying tissue tension in the granulosa layer after laser surgery","author":[{"full_name":"Xia, Peng","id":"4AB6C7D0-F248-11E8-B48F-1D18A9856A87","last_name":"Xia","first_name":"Peng","orcid":"0000-0002-5419-7756"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg"}],"publication_status":"published","year":"2021"},{"isi":1,"publication_status":"published","year":"2021","has_accepted_license":"1","date_published":"2021-05-24T00:00:00Z","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin"},{"last_name":"Schwarz","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A"},{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","full_name":"Basilico, Bernadette","last_name":"Basilico","first_name":"Bernadette","orcid":"0000-0003-1843-3173"},{"last_name":"Tasciyan","orcid":"0000-0003-1671-393X","first_name":"Saren","full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8370-6161","first_name":"Georgi A","last_name":"Dimchev","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","full_name":"Dimchev, Georgi A"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","first_name":"Armel","last_name":"Nicolas"},{"last_name":"Sommer","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M"},{"full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","last_name":"Kreuzinger"},{"last_name":"Dotter","orcid":"0000-0002-9033-9096","first_name":"Christoph","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Knaus","first_name":"Lisa","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","last_name":"Dobler","first_name":"Zoe"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078","first_name":"Florian KM","last_name":"Schur"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"}],"_id":"9429","publisher":"Springer Nature","article_processing_charge":"No","external_id":{"isi":["000658769900010"]},"issue":"1","article_number":"3058","quality_controlled":"1","keyword":["General Biochemistry","Genetics and Molecular Biology"],"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","status":"public","intvolume":"        12","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"publication":"Nature Communications","volume":12,"date_updated":"2026-09-12T22:30:13Z","date_created":"2021-05-28T11:49:46Z","doi":"10.1038/s41467-021-23123-x","month":"05","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","corr_author":"1","ddc":["572"],"oa_version":"Published Version","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"19557"},{"id":"7800","relation":"earlier_version","status":"public"},{"status":"public","relation":"dissertation_contains","id":"12401"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/"}]},"project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"grant_number":"715508","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"name":"Molecular Drug Targets","grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem cells in autism and epilepsy","grant_number":"F7807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"}],"department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"ec_funded":1,"type":"journal_article","oa":1,"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"},"fulldoi":"https://doi.org/10.1038/s41467-021-23123-x","acknowledged_ssus":[{"_id":"PreCl"}],"citation":{"short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>.","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>"},"publication_identifier":{"eissn":["2041-1723"]},"file":[{"success":1,"access_level":"open_access","file_id":"9430","file_size":9358599,"file_name":"2021_NatureCommunications_Morandell.pdf","date_updated":"2021-05-28T12:39:43Z","date_created":"2021-05-28T12:39:43Z","relation":"main_file","creator":"kschuh","content_type":"application/pdf","checksum":"337e0f7959c35ec959984cacdcb472ba"}],"file_date_updated":"2021-05-28T12:39:43Z","article_type":"original","day":"24"},{"page":"73","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"10316"}]},"type":"dissertation","department":[{"_id":"MiSi"},{"_id":"CaGu"},{"_id":"GradSch"}],"date_updated":"2026-07-06T12:48:19Z","date_created":"2021-11-18T15:05:06Z","doi":"10.15479/at:ista:10307","ddc":["570"],"oa_version":"Published Version","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","corr_author":"1","month":"11","file_date_updated":"2022-12-20T23:30:05Z","file":[{"file_name":"ThesisTomasekKathrin.pdf","file_size":13266088,"embargo":"2022-11-18","file_id":"10308","date_created":"2021-11-18T15:07:31Z","relation":"main_file","date_updated":"2022-12-20T23:30:05Z","content_type":"application/pdf","creator":"ktomasek","checksum":"b39c9e0ef18d0484d537a67551effd02","access_level":"open_access"},{"embargo_to":"open_access","access_level":"closed","file_id":"10309","file_size":7539509,"file_name":"ThesisTomasekKathrin.docx","date_created":"2021-11-18T15:07:46Z","relation":"source_file","date_updated":"2022-12-20T23:30:05Z","creator":"ktomasek","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"c0c440ee9e5ef1102a518a4f9f023e7c"}],"day":"18","OA_place":"publisher","oa":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"fulldoi":"https://doi.org/10.15479/at:ista:10307","publication_identifier":{"issn":["2663-337X"]},"citation":{"ista":"Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria.","chicago":"Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.” Institute of Science and Technology Austria, 2021. <a href=\"https://doi.org/10.15479/at:ista:10307\">https://doi.org/10.15479/at:ista:10307</a>.","short":"K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response, Institute of Science and Technology Austria, 2021.","ama":"Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021. doi:<a href=\"https://doi.org/10.15479/at:ista:10307\">10.15479/at:ista:10307</a>","mla":"Tomasek, Kathrin. <i>Pathogenic Escherichia Coli Hijack the Host Immune Response</i>. Institute of Science and Technology Austria, 2021, doi:<a href=\"https://doi.org/10.15479/at:ista:10307\">10.15479/at:ista:10307</a>.","ieee":"K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021.","apa":"Tomasek, K. (2021). <i>Pathogenic Escherichia coli hijack the host immune response</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:10307\">https://doi.org/10.15479/at:ista:10307</a>"},"supervisor":[{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-4561-241X"},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"date_published":"2021-11-18T00:00:00Z","title":"Pathogenic Escherichia coli hijack the host immune response","author":[{"last_name":"Tomasek","first_name":"Kathrin","orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"}],"has_accepted_license":"1","year":"2021","publication_status":"published","abstract":[{"lang":"eng","text":"Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response."}],"language":[{"iso":"eng"}],"status":"public","publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","_id":"10307","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD"},{"related_material":{"record":[{"relation":"later_version","status":"public","id":"11843"},{"id":"10307","status":"public","relation":"dissertation_contains"}]},"project":[{"grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients"},{"name":"Mechanical adaptation of lamellipodial actin","grant_number":"P29911","_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"ec_funded":1,"department":[{"_id":"CaGu"},{"_id":"MiSi"}],"type":"preprint","date_created":"2021-11-19T12:24:16Z","doi":"10.1101/2021.10.18.464770","date_updated":"2026-09-12T22:30:30Z","month":"10","oa_version":"Preprint","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"18","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1","open_access":"1"}],"oa":1,"citation":{"ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>bioRxiv</i>. .","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, <a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>."},"fulldoi":"https://doi.org/10.1101/2021.10.18.464770","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"date_published":"2021-10-18T00:00:00Z","author":[{"id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","first_name":"Kathrin","last_name":"Tomasek"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","orcid":"0000-0002-1073-744X","last_name":"Leithner"},{"full_name":"Glatzová, Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","last_name":"Glatzová","first_name":"Ivana"},{"first_name":"Michael S.","last_name":"Lukesch","full_name":"Lukesch, Michael S."},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-4561-241X"}],"title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","publication_status":"draft","year":"2021","abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"status":"public","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","language":[{"iso":"eng"}],"publication":"bioRxiv","_id":"10316","article_processing_charge":"No","das_tickbox":"1"},{"article_type":"original","day":"08","file":[{"checksum":"a24ec24e38d843341ae620ec76c53688","content_type":"application/pdf","creator":"dernst","relation":"main_file","date_created":"2020-05-11T11:34:08Z","date_updated":"2020-07-14T12:48:03Z","file_size":1402146,"file_name":"2020_FrontiersEduc_Beattie.pdf","file_id":"7818","access_level":"open_access"}],"file_date_updated":"2020-07-14T12:48:03Z","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/10.3389/feduc.2020.00048","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"publication_identifier":{"issn":["2504-284X"]},"citation":{"apa":"Beattie, R. J., Hippenmeyer, S., &#38; Pauler, F. (2020). SCOPES: Sparking curiosity through Open-Source platforms in education and science. <i>Frontiers in Education</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/feduc.2020.00048\">https://doi.org/10.3389/feduc.2020.00048</a>","ieee":"R. J. Beattie, S. Hippenmeyer, and F. Pauler, “SCOPES: Sparking curiosity through Open-Source platforms in education and science,” <i>Frontiers in Education</i>, vol. 5. Frontiers Media, 2020.","mla":"Beattie, Robert J., et al. “SCOPES: Sparking Curiosity through Open-Source Platforms in Education and Science.” <i>Frontiers in Education</i>, vol. 5, 48, Frontiers Media, 2020, doi:<a href=\"https://doi.org/10.3389/feduc.2020.00048\">10.3389/feduc.2020.00048</a>.","ama":"Beattie RJ, Hippenmeyer S, Pauler F. SCOPES: Sparking curiosity through Open-Source platforms in education and science. <i>Frontiers in Education</i>. 2020;5. doi:<a href=\"https://doi.org/10.3389/feduc.2020.00048\">10.3389/feduc.2020.00048</a>","chicago":"Beattie, Robert J, Simon Hippenmeyer, and Florian Pauler. “SCOPES: Sparking Curiosity through Open-Source Platforms in Education and Science.” <i>Frontiers in Education</i>. Frontiers Media, 2020. <a href=\"https://doi.org/10.3389/feduc.2020.00048\">https://doi.org/10.3389/feduc.2020.00048</a>.","ista":"Beattie RJ, Hippenmeyer S, Pauler F. 2020. SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. 5, 48.","short":"R.J. Beattie, S. Hippenmeyer, F. Pauler, Frontiers in Education 5 (2020)."},"oa":1,"scopus_import":"1","department":[{"_id":"SiHi"}],"ec_funded":1,"type":"journal_article","project":[{"grant_number":"M02416","_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"month":"05","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","ddc":["570"],"date_updated":"2024-10-22T10:46:38Z","doi":"10.3389/feduc.2020.00048","date_created":"2020-05-11T08:18:48Z","publication":"Frontiers in Education","volume":5,"intvolume":"         5","language":[{"iso":"eng"}],"status":"public","abstract":[{"text":"Scientific research is to date largely restricted to wealthy laboratories in developed nations due to the necessity of complex and expensive equipment. This inequality limits the capacity of science to be used as a diplomatic channel. Maker movements use open-source technologies including additive manufacturing (3D printing) and laser cutting, together with low-cost computers for developing novel products. This movement is setting the groundwork for a revolution, allowing scientific equipment to be sourced at a fraction of the cost and has the potential to increase the availability of equipment for scientists around the world. Science education is increasingly recognized as another channel for science diplomacy. In this perspective, we introduce the idea that the Maker movement and open-source technologies have the potential to revolutionize science, technology, engineering and mathematics (STEM) education worldwide. We present an open-source STEM didactic tool called SCOPES (Sparking Curiosity through Open-source Platforms in Education and Science). SCOPES is self-contained, independent of local resources, and cost-effective. SCOPES can be adapted to communicate complex subjects from genetics to neurobiology, perform real-world biological experiments and explore digitized scientific samples. We envision such platforms will enhance science diplomacy by providing a means for scientists to share their findings with classrooms and for educators to incorporate didactic concepts into STEM lessons. By providing students the opportunity to design, perform, and share scientific experiments, students also experience firsthand the benefits of a multinational scientific community. We provide instructions on how to build and use SCOPES on our webpage: http://scopeseducation.org.","lang":"eng"}],"article_number":"48","quality_controlled":"1","_id":"7814","article_processing_charge":"No","publisher":"Frontiers Media","title":"SCOPES: Sparking curiosity through Open-Source platforms in education and science","author":[{"full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","last_name":"Beattie","orcid":"0000-0002-8483-8753","first_name":"Robert J"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"},{"first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"}],"date_published":"2020-05-08T00:00:00Z","publication_status":"published","year":"2020","has_accepted_license":"1"},{"scopus_import":"1","oa":1,"citation":{"ieee":"A. Kopf <i>et al.</i>, “Microtubules control cellular shape and coherence in amoeboid migrating cells,” <i>The Journal of Cell Biology</i>, vol. 219, no. 6. Rockefeller University Press, 2020.","apa":"Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin, J., … Sixt, M. K. (2020). Microtubules control cellular shape and coherence in amoeboid migrating cells. <i>The Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.201907154\">https://doi.org/10.1083/jcb.201907154</a>","mla":"Kopf, Aglaja, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” <i>The Journal of Cell Biology</i>, vol. 219, no. 6, e201907154, Rockefeller University Press, 2020, doi:<a href=\"https://doi.org/10.1083/jcb.201907154\">10.1083/jcb.201907154</a>.","ama":"Kopf A, Renkawitz J, Hauschild R, et al. Microtubules control cellular shape and coherence in amoeboid migrating cells. <i>The Journal of Cell Biology</i>. 2020;219(6). doi:<a href=\"https://doi.org/10.1083/jcb.201907154\">10.1083/jcb.201907154</a>","short":"A. Kopf, J. Renkawitz, R. Hauschild, I. Girkontaite, K. Tedford, J. Merrin, O. Thorn-Seshold, D. Trauner, H. Häcker, K.D. Fischer, E. Kiermaier, M.K. Sixt, The Journal of Cell Biology 219 (2020).","chicago":"Kopf, Aglaja, Jörg Renkawitz, Robert Hauschild, Irute Girkontaite, Kerry Tedford, Jack Merrin, Oliver Thorn-Seshold, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” <i>The Journal of Cell Biology</i>. Rockefeller University Press, 2020. <a href=\"https://doi.org/10.1083/jcb.201907154\">https://doi.org/10.1083/jcb.201907154</a>.","ista":"Kopf A, Renkawitz J, Hauschild R, Girkontaite I, Tedford K, Merrin J, Thorn-Seshold O, Trauner D, Häcker H, Fischer KD, Kiermaier E, Sixt MK. 2020. Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. 219(6), e201907154."},"fulldoi":"https://doi.org/10.1083/jcb.201907154","publication_identifier":{"eissn":["1540-8140"]},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_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"},"file_date_updated":"2020-11-24T13:25:13Z","file":[{"success":1,"access_level":"open_access","relation":"main_file","date_updated":"2020-11-24T13:25:13Z","date_created":"2020-11-24T13:25:13Z","file_name":"2020_JCellBiol_Kopf.pdf","file_size":7536712,"file_id":"8801","checksum":"cb0b9c77842ae1214caade7b77e4d82d","content_type":"application/pdf","creator":"dernst"}],"day":"01","article_type":"original","date_updated":"2025-04-14T13:10:03Z","doi":"10.1083/jcb.201907154","date_created":"2020-05-24T22:00:56Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","corr_author":"1","ddc":["570"],"oa_version":"Published Version","month":"06","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"},{"name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373"},{"name":"Mechanical adaptation of lamellipodial actin","grant_number":"P29911","call_identifier":"FWF","_id":"26018E70-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1250-B20","_id":"252C3B08-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Nano-Analytics of Cellular Systems"},{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014","name":"Molecular and system level view of immune cell migration"}],"pmid":1,"type":"journal_article","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"ec_funded":1,"publisher":"Rockefeller University Press","article_processing_charge":"No","_id":"7875","quality_controlled":"1","external_id":{"isi":["000538141100020"],"pmid":["32379884"]},"article_number":"e201907154","issue":"6","language":[{"iso":"eng"}],"acknowledgement":"The authors thank the Scientific Service Units (Life Sciences, Bioimaging, Preclinical) of the Institute of Science and Technology Austria for excellent support. This work was funded by the European Research Council (ERC StG 281556 and CoG 724373), two grants from the Austrian\r\nScience Fund (FWF; P29911 and DK Nanocell W1250-B20 to M. Sixt) and by the German Research Foundation (DFG SFB1032 project B09) to O. Thorn-Seshold and D. Trauner. J. Renkawitz was supported by ISTFELLOW funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under the Research Executive Agency grant agreement (291734) and a European Molecular Biology Organization long-term fellowship (ALTF 1396-2014) co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409), E. Kiermaier by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2151—390873048, and H. Hacker by the American Lebanese Syrian Associated ¨Charities. K.-D. Fischer was supported by the Analysis, Imaging and Modelling of Neuronal and Inflammatory Processes graduate school funded by the Ministry of Economics, Science, and Digitisation of the State Saxony-Anhalt and by the European Funds for Social and Regional Development.","intvolume":"       219","status":"public","abstract":[{"lang":"eng","text":"Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence."}],"publication":"The Journal of Cell Biology","volume":219,"isi":1,"year":"2020","has_accepted_license":"1","publication_status":"published","date_published":"2020-06-01T00:00:00Z","title":"Microtubules control cellular shape and coherence in amoeboid migrating cells","author":[{"last_name":"Kopf","orcid":"0000-0002-2187-6656","first_name":"Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","full_name":"Kopf, Aglaja"},{"full_name":"Renkawitz, Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","first_name":"Jörg","orcid":"0000-0003-2856-3369","last_name":"Renkawitz"},{"first_name":"Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Girkontaite, Irute","last_name":"Girkontaite","first_name":"Irute"},{"first_name":"Kerry","last_name":"Tedford","full_name":"Tedford, Kerry"},{"first_name":"Jack","orcid":"0000-0001-5145-4609","last_name":"Merrin","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Thorn-Seshold","first_name":"Oliver","full_name":"Thorn-Seshold, Oliver"},{"first_name":"Dirk","last_name":"Trauner","full_name":"Trauner, Dirk","id":"E8F27F48-3EBA-11E9-92A1-B709E6697425"},{"last_name":"Häcker","first_name":"Hans","full_name":"Häcker, Hans"},{"full_name":"Fischer, Klaus Dieter","first_name":"Klaus Dieter","last_name":"Fischer"},{"full_name":"Kiermaier, Eva","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87","last_name":"Kiermaier","first_name":"Eva","orcid":"0000-0001-6165-5738"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}]},{"publication":"Neuron","volume":107,"acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo for comments on earlier versions of the manuscript. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031). R.B. received support from the FWF Meitner-Programm (M 2416). This work was also supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement 618444 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","language":[{"iso":"eng"}],"intvolume":"       107","status":"public","abstract":[{"text":"In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity.","lang":"eng"}],"external_id":{"isi":["000579698700006"],"pmid":["32707083"]},"issue":"6","quality_controlled":"1","_id":"8162","publisher":"Elsevier","article_processing_charge":"No","author":[{"id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne","orcid":"0000-0002-7903-3010","first_name":"Susanne","last_name":"Laukoter"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler"},{"last_name":"Beattie","orcid":"0000-0002-8483-8753","first_name":"Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","full_name":"Beattie, Robert J"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","last_name":"Amberg","orcid":"0000-0002-3183-8207","first_name":"Nicole"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H","last_name":"Hansen","first_name":"Andi H"},{"last_name":"Streicher","first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Thomas","last_name":"Penz","full_name":"Penz, Thomas"},{"full_name":"Bock, Christoph","last_name":"Bock","first_name":"Christoph","orcid":"0000-0001-6091-3088"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"title":"Cell-type specificity of genomic imprinting in cerebral cortex","date_published":"2020-09-23T00:00:00Z","publication_status":"published","year":"2020","has_accepted_license":"1","isi":1,"article_type":"original","day":"23","file":[{"file_name":"2020_Neuron_Laukoter.pdf","file_size":8911830,"file_id":"8828","date_updated":"2020-12-02T09:26:46Z","date_created":"2020-12-02T09:26:46Z","relation":"main_file","content_type":"application/pdf","creator":"dernst","checksum":"7becdc16a6317304304631087ae7dd7f","success":1,"access_level":"open_access"}],"file_date_updated":"2020-12-02T09:26:46Z","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"fulldoi":"https://doi.org/10.1016/j.neuron.2020.06.031","citation":{"short":"S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher, T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.","chicago":"Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>.","ista":"Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T, Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 107(6), 1160–1179.e9.","apa":"Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher, C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>","ieee":"S. Laukoter <i>et al.</i>, “Cell-type specificity of genomic imprinting in cerebral cortex,” <i>Neuron</i>, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.","mla":"Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>.","ama":"Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. 2020;107(6):1160-1179.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"publication_identifier":{"issn":["0896-6273"]},"scopus_import":"1","oa":1,"department":[{"_id":"SiHi"}],"ec_funded":1,"type":"journal_article","related_material":{"link":[{"description":"News on IST Website","relation":"press_release","url":"https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/"}]},"pmid":1,"project":[{"name":"Molecular mechanisms of radial neuronal migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812"},{"name":"Role of Eed in neural stem cell lineage progression","grant_number":"T01031","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"},{"grant_number":"M02416","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"},{"_id":"25D7962E-B435-11E9-9278-68D0E5697425","grant_number":"RGP0053/2014","name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level"},{"_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"}],"page":"1160-1179.e9","month":"09","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","oa_version":"Published Version","ddc":["570"],"date_created":"2020-07-23T16:03:12Z","doi":"10.1016/j.neuron.2020.06.031","date_updated":"2025-06-12T07:19:46Z"},{"ec_funded":1,"department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"type":"journal_article","pmid":1,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/the-bouncer-in-the-brain/","relation":"press_release","description":"News on IST Website"}]},"project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"page":"1212-1225","month":"09","oa_version":"Published Version","ddc":["570"],"corr_author":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2025-04-15T08:29:03Z","doi":"10.1016/j.neuron.2020.07.006","date_created":"2020-08-14T09:36:05Z","article_type":"original","day":"23","file":[{"success":1,"access_level":"open_access","file_size":3011120,"file_name":"2020_Neuron_Zhang.pdf","file_id":"8920","date_updated":"2020-12-04T09:29:21Z","relation":"main_file","date_created":"2020-12-04T09:29:21Z","content_type":"application/pdf","creator":"dernst","checksum":"44a5960fc083a4cb3488d22224859fdc"}],"file_date_updated":"2020-12-04T09:29:21Z","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"fulldoi":"https://doi.org/10.1016/j.neuron.2020.07.006","publication_identifier":{"issn":["0896-6273"]},"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"ScienComp"},{"_id":"PreCl"}],"citation":{"short":"X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225.","ista":"Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. 107(6), 1212–1225.","chicago":"Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">https://doi.org/10.1016/j.neuron.2020.07.006</a>.","ama":"Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow from input to output in hippocampal granule cells. <i>Neuron</i>. 2020;107(6):1212-1225. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">10.1016/j.neuron.2020.07.006</a>","ieee":"X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information flow from input to output in hippocampal granule cells,” <i>Neuron</i>, vol. 107, no. 6. Elsevier, pp. 1212–1225, 2020.","apa":"Zhang, X., Schlögl, A., &#38; Jonas, P. M. (2020). Selective routing of spatial information flow from input to output in hippocampal granule cells. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">https://doi.org/10.1016/j.neuron.2020.07.006</a>","mla":"Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” <i>Neuron</i>, vol. 107, no. 6, Elsevier, 2020, pp. 1212–25, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">10.1016/j.neuron.2020.07.006</a>."},"oa":1,"scopus_import":"1","author":[{"first_name":"Xiaomin","last_name":"Zhang","full_name":"Zhang, Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","full_name":"Schlögl, Alois","last_name":"Schlögl","orcid":"0000-0002-5621-8100","first_name":"Alois"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"title":"Selective routing of spatial information flow from input to output in hippocampal granule cells","date_published":"2020-09-23T00:00:00Z","publication_status":"published","has_accepted_license":"1","year":"2020","isi":1,"volume":107,"publication":"Neuron","abstract":[{"lang":"eng","text":"Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion."}],"status":"public","acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari, Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp recording. We are grateful to Florian Marr for cell labeling, cell reconstruction, and technical assistance; Ben Suter for helpful discussions; Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor Asenov (Machine Shop) for device construction. We also thank the Scientific Service Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical Facility) for efficient support.","language":[{"iso":"eng"}],"intvolume":"       107","issue":"6","external_id":{"pmid":["32763145"],"isi":["000579698700009"]},"quality_controlled":"1","_id":"8261","publisher":"Elsevier","article_processing_charge":"No"},{"year":"2020","has_accepted_license":"1","publication_status":"published","date_published":"2020-12-18T00:00:00Z","author":[{"id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne","orcid":"0000-0002-7903-3010","first_name":"Susanne","last_name":"Laukoter"},{"full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207"},{"last_name":"Pauler","first_name":"Florian","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer"}],"title":"Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy","publisher":"Elsevier","article_processing_charge":"No","_id":"8978","quality_controlled":"1","external_id":{"pmid":["33377108"]},"article_number":"100215","issue":"3","language":[{"iso":"eng"}],"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). N.A received support from the FWF Firnberg-Programm (T 1031). This work was also supported by IST Austria institutional funds; FWF SFB F78 to S.H.; NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) 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.","intvolume":"         1","status":"public","abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) technology enables concomitant fluorescent cell labeling and induction of uniparental chromosome disomy (UPD) with single-cell resolution. In UPD, imprinted genes are either overexpressed 2-fold or are not expressed. Here, the MADM platform is utilized to probe imprinting phenotypes at the transcriptional level. This protocol highlights major steps for the generation and isolation of projection neurons and astrocytes with MADM-induced UPD from mouse cerebral cortex for downstream single-cell and low-input sample RNA-sequencing experiments.\r\n\r\nFor complete details on the use and execution of this protocol, please refer to Laukoter et al. (2020b)."}],"publication":"STAR Protocols","volume":1,"doi":"10.1016/j.xpro.2020.100215","date_created":"2020-12-30T10:17:07Z","date_updated":"2025-04-15T08:23:06Z","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"oa_version":"Published Version","month":"12","project":[{"name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"T01031"},{"_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"},{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002"},{"grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","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"}],"pmid":1,"type":"journal_article","department":[{"_id":"SiHi"}],"ec_funded":1,"oa":1,"scopus_import":"1","publication_identifier":{"issn":["2666-1667"]},"fulldoi":"https://doi.org/10.1016/j.xpro.2020.100215","citation":{"ieee":"S. Laukoter, N. Amberg, F. Pauler, and S. Hippenmeyer, “Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy,” <i>STAR Protocols</i>, vol. 1, no. 3. Elsevier, 2020.","apa":"Laukoter, S., Amberg, N., Pauler, F., &#38; Hippenmeyer, S. (2020). Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">https://doi.org/10.1016/j.xpro.2020.100215</a>","mla":"Laukoter, Susanne, et al. “Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome Disomy.” <i>STAR Protocols</i>, vol. 1, no. 3, 100215, Elsevier, 2020, doi:<a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">10.1016/j.xpro.2020.100215</a>.","ama":"Laukoter S, Amberg N, Pauler F, Hippenmeyer S. Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. <i>STAR Protocols</i>. 2020;1(3). doi:<a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">10.1016/j.xpro.2020.100215</a>","short":"S. Laukoter, N. Amberg, F. Pauler, S. Hippenmeyer, STAR Protocols 1 (2020).","chicago":"Laukoter, Susanne, Nicole Amberg, Florian Pauler, and Simon Hippenmeyer. “Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome Disomy.” <i>STAR Protocols</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">https://doi.org/10.1016/j.xpro.2020.100215</a>.","ista":"Laukoter S, Amberg N, Pauler F, Hippenmeyer S. 2020. Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. STAR Protocols. 1(3), 100215."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"file_date_updated":"2021-01-07T15:57:27Z","file":[{"checksum":"f1e9a433e9cb0f41f7b6df6b76db1f6e","creator":"dernst","content_type":"application/pdf","relation":"main_file","date_created":"2021-01-07T15:57:27Z","date_updated":"2021-01-07T15:57:27Z","file_id":"8996","file_name":"2020_STARProtocols_Laukoter.pdf","file_size":4031449,"access_level":"open_access","success":1}],"day":"18","article_type":"original"},{"volume":11,"publication":"Nature Communications","abstract":[{"lang":"eng","text":"The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor cell and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype."}],"status":"public","language":[{"iso":"eng"}],"intvolume":"        11","quality_controlled":"1","article_number":"195","external_id":{"pmid":["31924768"],"isi":["000551459000005"]},"publisher":"Springer Nature","article_processing_charge":"No","_id":"7253","title":"Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development","author":[{"last_name":"Laukoter","orcid":"0000-0002-7903-3010","first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne"},{"first_name":"Robert J","orcid":"0000-0002-8483-8753","last_name":"Beattie","full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler"},{"full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg"},{"last_name":"Nakayama","first_name":"Keiichi I.","full_name":"Nakayama, Keiichi I."},{"orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"date_published":"2020-01-10T00:00:00Z","has_accepted_license":"1","year":"2020","publication_status":"published","isi":1,"day":"10","article_type":"original","file_date_updated":"2020-07-14T12:47:54Z","file":[{"relation":"main_file","date_created":"2020-01-13T07:42:31Z","date_updated":"2020-07-14T12:47:54Z","file_size":8063333,"file_name":"2020_NatureComm_Laukoter.pdf","file_id":"7261","checksum":"ebf1ed522f4e0be8d94c939c1806a709","content_type":"application/pdf","creator":"dernst","access_level":"open_access"}],"fulldoi":"https://doi.org/10.1038/s41467-019-14077-2","citation":{"ama":"Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. <i>Nature Communications</i>. 2020;11. doi:<a href=\"https://doi.org/10.1038/s41467-019-14077-2\">10.1038/s41467-019-14077-2</a>","mla":"Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” <i>Nature Communications</i>, vol. 11, 195, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1038/s41467-019-14077-2\">10.1038/s41467-019-14077-2</a>.","ieee":"S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer, “Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development,” <i>Nature Communications</i>, vol. 11. Springer Nature, 2020.","apa":"Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., &#38; Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-019-14077-2\">https://doi.org/10.1038/s41467-019-14077-2</a>","short":"S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer, Nature Communications 11 (2020).","ista":"Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. 2020. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 11, 195.","chicago":"Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” <i>Nature Communications</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41467-019-14077-2\">https://doi.org/10.1038/s41467-019-14077-2</a>."},"publication_identifier":{"issn":["2041-1723"]},"acknowledged_ssus":[{"_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"},"scopus_import":"1","oa":1,"type":"journal_article","ec_funded":1,"department":[{"_id":"SiHi"}],"project":[{"call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T01031","name":"Role of Eed in neural stem cell lineage progression"},{"grant_number":"M02416","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"},{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"}],"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/"}]},"pmid":1,"ddc":["570"],"oa_version":"Published Version","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"01","date_updated":"2025-06-12T07:30:49Z","date_created":"2020-01-11T10:42:48Z","doi":"10.1038/s41467-019-14077-2"},{"language":[{"iso":"eng"}],"status":"public","abstract":[{"lang":"eng","text":"Beginning from a limited pool of progenitors, the mammalian cerebral cortex forms highly organized functional neural circuits. However, the underlying cellular and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs) and eventual production of neurons and glia in the developing neuroepithelium remains unclear. Methods to trace NSC division patterns and map the lineage of clonally related cells have advanced dramatically. However, many contemporary lineage tracing techniques suffer from the lack of cellular resolution of progeny cell fate, which is essential for deciphering progenitor cell division patterns. Presented is a protocol using mosaic analysis with double markers (MADM) to perform in vivo clonal analysis. MADM concomitantly manipulates individual progenitor cells and visualizes precise division patterns and lineage progression at unprecedented single cell resolution. MADM-based interchromosomal recombination events during the G2-X phase of mitosis, together with temporally inducible CreERT2, provide exact information on the birth dates of clones and their division patterns. Thus, MADM lineage tracing provides unprecedented qualitative and quantitative optical readouts of the proliferation mode of stem cell progenitors at the single cell level. MADM also allows for examination of the mechanisms and functional requirements of candidate genes in NSC lineage progression. This method is unique in that comparative analysis of control and mutant subclones can be performed in the same tissue environment in vivo. Here, the protocol is described in detail, and experimental paradigms to employ MADM for clonal analysis and lineage tracing in the developing cerebral cortex are demonstrated. Importantly, this protocol can be adapted to perform MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver is present."}],"publication":"Journal of Visual Experiments","_id":"7815","article_processing_charge":"No","publisher":"MyJove Corporation","external_id":{"isi":["000546406600043"],"pmid":["32449730"]},"article_number":"e61147","issue":"159","quality_controlled":"1","date_published":"2020-05-08T00:00:00Z","author":[{"full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8483-8753","first_name":"Robert J","last_name":"Beattie"},{"first_name":"Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207"},{"last_name":"Cheung","first_name":"Giselle T","orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T"},{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","last_name":"Contreras","first_name":"Ximena"},{"first_name":"Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"title":"Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM)","isi":1,"publication_status":"published","year":"2020","has_accepted_license":"1","file":[{"access_level":"open_access","creator":"rbeattie","content_type":"application/pdf","checksum":"3154ea7f90b9fb45e084cd1c2770597d","file_id":"7816","file_size":1352186,"file_name":"jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf","date_created":"2020-05-11T08:28:38Z","date_updated":"2020-07-14T12:48:03Z","relation":"main_file"}],"file_date_updated":"2020-07-14T12:48:03Z","article_type":"original","day":"08","oa":1,"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"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"fulldoi":"https://doi.org/10.3791/61147","citation":{"apa":"Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen, A. H., &#38; Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). <i>Journal of Visual Experiments</i>. MyJove Corporation. <a href=\"https://doi.org/10.3791/61147\">https://doi.org/10.3791/61147</a>","mla":"Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” <i>Journal of Visual Experiments</i>, no. 159, e61147, MyJove Corporation, 2020, doi:<a href=\"https://doi.org/10.3791/61147\">10.3791/61147</a>.","ieee":"R. J. Beattie <i>et al.</i>, “Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM),” <i>Journal of Visual Experiments</i>, no. 159. MyJove Corporation, 2020.","ama":"Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). <i>Journal of Visual Experiments</i>. 2020;(159). doi:<a href=\"https://doi.org/10.3791/61147\">10.3791/61147</a>","chicago":"Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” <i>Journal of Visual Experiments</i>. MyJove Corporation, 2020. <a href=\"https://doi.org/10.3791/61147\">https://doi.org/10.3791/61147</a>.","ista":"Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159), e61147.","short":"R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen, S. Hippenmeyer, Journal of Visual Experiments (2020)."},"publication_identifier":{"issn":["1940-087X"]},"related_material":{"record":[{"id":"7902","relation":"part_of_dissertation","status":"public"}]},"pmid":1,"project":[{"_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"},{"grant_number":"T01031","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425","name":"Role of Eed in neural stem cell lineage progression"},{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"name":"Molecular mechanisms of radial neuronal migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"SiHi"}],"ec_funded":1,"type":"journal_article","doi":"10.3791/61147","date_updated":"2026-09-12T22:30:21Z","date_created":"2020-05-11T08:31:20Z","month":"05","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"oa_version":"Published Version"},{"department":[{"_id":"SiHi"}],"ec_funded":1,"type":"dissertation","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"28"},{"id":"7815","status":"public","relation":"dissertation_contains"},{"id":"6830","relation":"dissertation_contains","status":"public"}]},"project":[{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"page":"214","month":"06","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","corr_author":"1","ddc":["570"],"oa_version":"Published Version","date_created":"2020-05-29T08:27:32Z","date_updated":"2026-06-18T19:12:39Z","doi":"10.15479/AT:ISTA:7902","day":"05","file":[{"checksum":"43c172bf006c95b65992d473c7240d13","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"xcontreras","date_updated":"2021-06-07T22:30:03Z","relation":"source_file","date_created":"2020-06-05T08:18:08Z","file_size":53134142,"file_name":"PhDThesis_Contreras.docx","file_id":"7927","access_level":"closed","embargo_to":"open_access"},{"date_created":"2020-06-05T08:18:07Z","date_updated":"2021-06-07T22:30:03Z","relation":"main_file","file_name":"PhDThesis_Contreras.pdf","embargo":"2021-06-06","file_size":35117191,"file_id":"7928","checksum":"addfed9128271be05cae3608e03a6ec0","content_type":"application/pdf","creator":"xcontreras","access_level":"open_access"}],"file_date_updated":"2021-06-07T22:30:03Z","fulldoi":"https://doi.org/10.15479/AT:ISTA:7902","supervisor":[{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"}],"citation":{"chicago":"Contreras, Ximena. “Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7902\">https://doi.org/10.15479/AT:ISTA:7902</a>.","ista":"Contreras X. 2020. Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria.","short":"X. Contreras, Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution, Institute of Science and Technology Austria, 2020.","mla":"Contreras, Ximena. <i>Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7902\">10.15479/AT:ISTA:7902</a>.","apa":"Contreras, X. (2020). <i>Genetic dissection of neural development in health and disease at single cell resolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7902\">https://doi.org/10.15479/AT:ISTA:7902</a>","ieee":"X. Contreras, “Genetic dissection of neural development in health and disease at single cell resolution,” Institute of Science and Technology Austria, 2020.","ama":"Contreras X. Genetic dissection of neural development in health and disease at single cell resolution. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7902\">10.15479/AT:ISTA:7902</a>"},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"publication_identifier":{"issn":["2663-337X"]},"oa":1,"OA_place":"publisher","title":"Genetic dissection of neural development in health and disease at single cell resolution","author":[{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","first_name":"Ximena","last_name":"Contreras"}],"date_published":"2020-06-05T00:00:00Z","publication_status":"published","year":"2020","has_accepted_license":"1","language":[{"iso":"eng"}],"status":"public","abstract":[{"text":"Mosaic genetic analysis has been widely used in different model organisms such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific fashion. More recently, and less easily conducted, mosaic genetic analysis in mice has also been enabled with the ambition to shed light on human gene function and disease. These genetic tools are of particular interest, but not restricted to, the study of the brain. Notably, the MADM technology offers a genetic approach in mice to visualize and concomitantly manipulate small subsets of genetically defined cells at a clonal level and single cell resolution. MADM-based analysis has already advanced the study of genetic mechanisms regulating brain development and is expected that further MADM-based analysis of genetic alterations will continue to reveal important insights on the fundamental principles of development and disease to potentially assist in the development of new therapies or treatments.\r\nIn summary, this work completed and characterized the necessary genome-wide genetic tools to perform MADM-based analysis at single cell level of the vast majority of mouse genes in virtually any cell type and provided a protocol to perform lineage tracing using the novel MADM resource. Importantly, this work also explored and revealed novel aspects of biologically relevant events in an in vivo context, such as the chromosome-specific bias of chromatid sister segregation pattern, the generation of cell-type diversity in the cerebral cortex and in the cerebellum and finally, the relevance of the interplay between the cell-autonomous gene function and cell-non-autonomous (community) effects in radial glial progenitor lineage progression.\r\nThis work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation.","lang":"eng"}],"degree_awarded":"PhD","alternative_title":["ISTA Thesis"],"_id":"7902","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria"},{"type":"dissertation","department":[{"_id":"BjHo"},{"_id":"CaHe"}],"page":"107","related_material":{"record":[{"id":"7001","status":"public","relation":"part_of_dissertation"},{"id":"6508","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"735"},{"relation":"part_of_dissertation","status":"public","id":"661"}]},"oa_version":"None","ddc":["570"],"corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"09","date_created":"2020-09-09T11:12:10Z","date_updated":"2025-09-11T07:08:52Z","doi":"10.15479/AT:ISTA:8350","day":"09","file_date_updated":"2021-09-11T22:30:05Z","file":[{"file_id":"8351","file_size":65194814,"file_name":"Shayan-Thesis-Final.docx","relation":"source_file","date_updated":"2021-09-11T22:30:05Z","date_created":"2020-09-09T11:06:27Z","creator":"sshamip","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"6e47871c74f85008b9876112eb3fcfa1","embargo_to":"open_access","access_level":"closed"},{"access_level":"open_access","date_updated":"2021-09-11T22:30:05Z","date_created":"2020-09-09T11:06:13Z","relation":"main_file","file_id":"8352","file_size":23729605,"embargo":"2021-09-10","file_name":"Shayan-Thesis-Final.pdf","checksum":"1b44c57f04d7e8a6fe41b1c9c55a52a3","creator":"sshamip","content_type":"application/pdf"}],"fulldoi":"https://doi.org/10.15479/AT:ISTA:8350","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"EM-Fac"}],"publication_identifier":{"issn":["2663-337X"]},"citation":{"chicago":"Shamipour, Shayan. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes .” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8350\">https://doi.org/10.15479/AT:ISTA:8350</a>.","ista":"Shamipour S. 2020. Bulk actin dynamics drive phase segregation in zebrafish oocytes . Institute of Science and Technology Austria.","short":"S. Shamipour, Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes , Institute of Science and Technology Austria, 2020.","apa":"Shamipour, S. (2020). <i>Bulk actin dynamics drive phase segregation in zebrafish oocytes </i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8350\">https://doi.org/10.15479/AT:ISTA:8350</a>","mla":"Shamipour, Shayan. <i>Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes </i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8350\">10.15479/AT:ISTA:8350</a>.","ieee":"S. Shamipour, “Bulk actin dynamics drive phase segregation in zebrafish oocytes ,” Institute of Science and Technology Austria, 2020.","ama":"Shamipour S. Bulk actin dynamics drive phase segregation in zebrafish oocytes . 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8350\">10.15479/AT:ISTA:8350</a>"},"supervisor":[{"full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J"},{"id":"3A374330-F248-11E8-B48F-1D18A9856A87","full_name":"Hof, Björn","first_name":"Björn","orcid":"0000-0003-2057-2754","last_name":"Hof"}],"oa":1,"author":[{"first_name":"Shayan","last_name":"Shamipour","full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87"}],"title":"Bulk actin dynamics drive phase segregation in zebrafish oocytes ","date_published":"2020-09-09T00:00:00Z","has_accepted_license":"1","year":"2020","publication_status":"published","abstract":[{"lang":"eng","text":"Cytoplasm is a gel-like crowded environment composed of tens of thousands of macromolecules, organelles, cytoskeletal networks and cytosol. The structure of the cytoplasm is thought to be highly organized and heterogeneous due to the crowding of its constituents and their effective compartmentalization. In such an environment, the diffusive dynamics of the molecules is very restricted, an effect that is further amplified by clustering and anchoring of molecules. Despite the jammed nature of the cytoplasm at the microscopic scale, large-scale reorganization of cytoplasm is essential for important cellular functions, such as nuclear positioning and cell division. How such mesoscale reorganization of the cytoplasm is achieved, especially for very large cells such as oocytes or syncytial tissues that can span hundreds of micrometers in size, has only begun to be understood.\r\nIn this thesis, I focus on the recent advances in elucidating the molecular, cellular and biophysical principles underlying cytoplasmic organization across different scales, structures and species. First, I outline which of these principles have been identified by reductionist approaches, such as in vitro reconstitution assays, where boundary conditions and components can be modulated at ease. I then describe how the theoretical and experimental framework established in these reduced systems have been applied to their more complex in vivo counterparts, in particular oocytes and embryonic syncytial structures, and discuss how such complex biological systems can initiate symmetry breaking and establish patterning.\r\nSpecifically, I examine an example of large-scale reorganizations taking place in zebrafish embryos, where extensive cytoplasmic streaming leads to the segregation of cytoplasm from yolk granules along the animal-vegetal axis of the embryo. Using biophysical experimentation and theory, I investigate the forces underlying this process, to show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the embryo. This wave functions in segregation by both pulling cytoplasm animally and pushing yolk granules vegetally. Cytoplasm pulling is mediated by bulk actin network flows exerting friction forces on the cytoplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. This study defines a novel role of bulk actin polymerization waves in embryo polarization via cytoplasmic segregation. Lastly, I describe the cytoplasmic reorganizations taking place during zebrafish oocyte maturation, where the initial segregation of the cytoplasm and yolk granules occurs. Here, I demonstrate a previously uncharacterized wave of microtubule aster formation, traveling the oocyte along the animal-vegetal axis. Further research is required to determine the role of such microtubule structures in cytoplasmic reorganizations therein.\r\nCollectively, these studies provide further evidence for the coupling between cell cytoskeleton and cell cycle machinery, which can underlie a core self-organizing mechanism for orchestrating large-scale reorganizations in a cell-cycle-tunable manner, where the modulations of the force-generating machinery and cytoplasmic mechanics can be harbored to fulfill cellular functions."}],"status":"public","acknowledgement":"I would have had no fish and hence no results without our wonderful fish facility crew, Verena Mayer, Eva Schlegl, Andreas Mlak and Matthias Nowak. Special thanks to Verena for being always happy to help and dealing with our chaotic schedules in the lab. Danke auch, Verena, für deine Geduld, mit mir auf Deutsch zu sprechen. Das hat mir sehr geholfen.\r\nSpecial thanks to the Bioimaging and EM facilities at IST Austria for supporting us every day. Very special thanks would go to Robert Hauschild for his continuous support on data analysis and also to Jack Merrin for designing and building microfabricated chambers for the project and for the various discussions on making zebrafish extracts.","language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","_id":"8350"},{"OA_place":"publisher","oa":1,"fulldoi":"https://doi.org/10.15479/AT:ISTA:8620","publication_identifier":{"issn":["2663-337X"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"citation":{"mla":"Morandell, Jasmin. <i>Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8620\">10.15479/AT:ISTA:8620</a>.","apa":"Morandell, J. (2020). <i>Illuminating the role of Cul3 in autism spectrum disorder pathogenesis</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8620\">https://doi.org/10.15479/AT:ISTA:8620</a>","ieee":"J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,” Institute of Science and Technology Austria, 2020.","ama":"Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8620\">10.15479/AT:ISTA:8620</a>","chicago":"Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8620\">https://doi.org/10.15479/AT:ISTA:8620</a>.","ista":"Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria.","short":"J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis, Institute of Science and Technology Austria, 2020."},"supervisor":[{"orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2021-10-16T22:30:04Z","file":[{"access_level":"open_access","creator":"jmorande","content_type":"application/pdf","checksum":"7ee83e42de3e5ce2fedb44dff472f75f","file_id":"8621","file_size":16155786,"embargo":"2021-10-15","file_name":"Jasmin_Morandell_Thesis-2020_final.pdf","date_updated":"2021-10-16T22:30:04Z","date_created":"2020-10-07T14:41:49Z","relation":"main_file"},{"embargo_to":"open_access","access_level":"closed","file_id":"8622","file_size":24344152,"file_name":"Jasmin_Morandell_Thesis-2020_final.zip","relation":"source_file","date_created":"2020-10-07T14:45:07Z","date_updated":"2021-10-16T22:30:04Z","creator":"jmorande","content_type":"application/x-zip-compressed","checksum":"5e0464af453734210ce7aab7b4a92e3a"}],"day":"12","date_updated":"2026-08-12T09:55:08Z","doi":"10.15479/AT:ISTA:8620","date_created":"2020-10-07T14:53:13Z","ddc":["610"],"oa_version":"Published Version","corr_author":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"10","page":"138","project":[{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232","name":"Molecular Drug Targets"},{"_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F7807","name":"Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem cells in autism and epilepsy"}],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"7800"},{"relation":"part_of_dissertation","status":"public","id":"8131"}]},"type":"dissertation","department":[{"_id":"GaNo"}],"article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","_id":"8620","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","abstract":[{"text":"The development of the human brain occurs through a tightly regulated series of dynamic and adaptive processes during prenatal and postnatal life. A disruption of this strictly orchestrated series of events can lead to a number of neurodevelopmental conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common, etiologically and phenotypically heterogeneous group of disorders sharing the core symptoms of social interaction and communication deficits and restrictive and repetitive interests and behaviors. They are estimated to affect one in 59 individuals in the U.S. and, over the last three decades, mutations in more than a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet, for the vast majority of these ASD-risk genes their role during brain development and precise molecular function still remain elusive.\r\nDe novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In the study described here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display cortical lamination abnormalities due to defective migration of post-mitotic excitatory neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal cortical organization, Cul3 heterozygous deletion is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neural cells results in atypical organization of the actin mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult mice does not induce the majority of the behavioral defects observed in constitutive Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn conclusion, our data indicate that Cul3 plays a critical role in the regulation of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral abnormalities are primarily due to dosage sensitive Cul3 functions at early brain developmental stages.","lang":"eng"}],"acknowledgement":"I would like to especially thank Armel Nicolas from the Proteomics and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka, Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line maintenance and their great support.","language":[{"iso":"eng"}],"status":"public","has_accepted_license":"1","year":"2020","publication_status":"published","date_published":"2020-10-12T00:00:00Z","author":[{"first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"}],"title":"Illuminating the role of Cul3 in autism spectrum disorder pathogenesis"},{"das_tickbox":"1","_id":"7800","article_processing_charge":"No","publication":"bioRxiv","language":[{"iso":"eng"}],"status":"public","abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.","lang":"eng"}],"publication_status":"draft","year":"2020","has_accepted_license":"1","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","author":[{"full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","first_name":"Jasmin"},{"full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Lena A"},{"last_name":"Basilico","orcid":"0000-0003-1843-3173","first_name":"Bernadette","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren","first_name":"Saren","orcid":"0000-0003-1671-393X","last_name":"Tasciyan"},{"full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas","first_name":"Armel"},{"full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105"},{"full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger","first_name":"Caroline"},{"first_name":"Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","first_name":"Zoe","last_name":"Dobler"},{"last_name":"Cacci","first_name":"Emanuele","full_name":"Cacci, Emanuele"},{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"}],"date_published":"2020-01-11T00:00:00Z","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"fulldoi":"https://doi.org/10.1101/2020.01.10.902064 ","citation":{"ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>bioRxiv</i>. .","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>"},"acknowledged_ssus":[{"_id":"PreCl"}],"oa":1,"day":"11","file":[{"access_level":"open_access","file_id":"7801","file_size":2931370,"file_name":"2020.01.10.902064v1.full.pdf","relation":"main_file","date_created":"2020-05-05T14:31:19Z","date_updated":"2020-07-14T12:48:03Z","creator":"rsix","content_type":"application/pdf","checksum":"c6799ab5daba80efe8e2ed63c15f8c81"}],"file_date_updated":"2020-07-14T12:48:03Z","month":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","ddc":["570"],"oa_version":"Preprint","date_created":"2020-05-05T14:31:33Z","date_updated":"2026-09-12T22:31:17Z","doi":"10.1101/2020.01.10.902064 ","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"type":"preprint","related_material":{"record":[{"id":"9429","status":"public","relation":"later_version"},{"status":"public","relation":"dissertation_contains","id":"8620"}]},"project":[{"grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules"},{"name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232"}]},{"publication_identifier":{"eissn":["1097-4172"],"issn":["0092-8674"]},"fulldoi":"https://doi.org/10.1016/j.cell.2019.04.030","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"citation":{"chicago":"Shamipour, Shayan, Roland Kardos, Shi-lei Xue, Björn Hof, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes.” <i>Cell</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.04.030\">https://doi.org/10.1016/j.cell.2019.04.030</a>.","ista":"Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. 2019. Bulk actin dynamics drive phase segregation in zebrafish oocytes. Cell. 177(6), 1463–1479.e18.","short":"S. Shamipour, R. Kardos, S. Xue, B. Hof, E.B. Hannezo, C.-P.J. Heisenberg, Cell 177 (2019) 1463–1479.e18.","apa":"Shamipour, S., Kardos, R., Xue, S., Hof, B., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2019). Bulk actin dynamics drive phase segregation in zebrafish oocytes. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2019.04.030\">https://doi.org/10.1016/j.cell.2019.04.030</a>","ieee":"S. Shamipour, R. Kardos, S. Xue, B. Hof, E. B. Hannezo, and C.-P. J. Heisenberg, “Bulk actin dynamics drive phase segregation in zebrafish oocytes,” <i>Cell</i>, vol. 177, no. 6. Elsevier, p. 1463–1479.e18, 2019.","mla":"Shamipour, Shayan, et al. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes.” <i>Cell</i>, vol. 177, no. 6, Elsevier, 2019, p. 1463–1479.e18, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.04.030\">10.1016/j.cell.2019.04.030</a>.","ama":"Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. Bulk actin dynamics drive phase segregation in zebrafish oocytes. <i>Cell</i>. 2019;177(6):1463-1479.e18. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.04.030\">10.1016/j.cell.2019.04.030</a>"},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cell.2019.04.030"}],"oa":1,"scopus_import":"1","article_type":"original","day":"30","file":[{"checksum":"aea43726d80e35ce3885073a5f05c3e3","creator":"dernst","content_type":"application/pdf","relation":"main_file","date_created":"2020-10-21T07:22:34Z","date_updated":"2020-10-21T07:22:34Z","file_id":"8686","file_size":3356292,"file_name":"2019_Cell_Shamipour_accepted.pdf","access_level":"open_access","success":1}],"file_date_updated":"2020-10-21T07:22:34Z","month":"05","ddc":["570"],"oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2019-06-02T21:59:12Z","doi":"10.1016/j.cell.2019.04.030","date_updated":"2026-09-12T22:30:22Z","ec_funded":1,"department":[{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"BjHo"}],"type":"journal_article","pmid":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"8350"}],"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/how-the-cytoplasm-separates-from-the-yolk/"}]},"page":"1463-1479.e18","project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"FWF","_id":"268294B6-B435-11E9-9278-68D0E5697425","grant_number":"P31639","name":"Active mechano-chemical description of the cell cytoskeleton"}],"issue":"6","external_id":{"pmid":["31080065"],"isi":["000469415100013"]},"quality_controlled":"1","_id":"6508","article_processing_charge":"No","publisher":"Elsevier","volume":177,"publication":"Cell","abstract":[{"lang":"eng","text":"Segregation of maternal determinants within the oocyte constitutes the first step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming leads to the segregation of ooplasm from yolk granules along the animal-vegetal axis of the oocyte. Here, we show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the oocyte. This wave functions in segregation by both pulling ooplasm animally and pushing yolk granules vegetally. Using biophysical experimentation and theory, we show that ooplasm pulling is mediated by bulk actin network flows exerting friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. Our study defines a novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte polarization via ooplasmic segregation."}],"status":"public","intvolume":"       177","acknowledgement":"We would like to thank Pierre Recho, Guillaume Salbreux, and Silvia Grigolon for advice on the theory, Lila Solnica-Krezel for kindly providing us with zebrafish dachsous mutants, members of the Heisenberg and Hannezo groups for fruitful discussions, and the Bioimaging and zebrafish facilities at IST Austria for their continuous support. This project has received funding from the European Union (European Research Council Advanced Grant 742573 to C.P.H.) and from the Austrian Science Fund (FWF) (P 31639 to E.H.).","language":[{"iso":"eng"}],"publication_status":"published","has_accepted_license":"1","year":"2019","isi":1,"title":"Bulk actin dynamics drive phase segregation in zebrafish oocytes","author":[{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","full_name":"Shamipour, Shayan","first_name":"Shayan","last_name":"Shamipour"},{"last_name":"Kardos","first_name":"Roland","id":"4039350E-F248-11E8-B48F-1D18A9856A87","full_name":"Kardos, Roland"},{"last_name":"Xue","first_name":"Shi-lei","full_name":"Xue, Shi-lei","id":"31D2C804-F248-11E8-B48F-1D18A9856A87"},{"id":"3A374330-F248-11E8-B48F-1D18A9856A87","full_name":"Hof, Björn","orcid":"0000-0003-2057-2754","first_name":"Björn","last_name":"Hof"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","first_name":"Edouard B","last_name":"Hannezo"},{"full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566"}],"date_published":"2019-05-30T00:00:00Z"},{"fulldoi":"https://doi.org/10.1016/j.cell.2019.10.006","publication_identifier":{"eissn":["1097-4172"],"issn":["0092-8674"]},"citation":{"ieee":"C. Schwayer <i>et al.</i>, “Mechanosensation of tight junctions depends on ZO-1 phase separation and flow,” <i>Cell</i>, vol. 179, no. 4. Cell Press, p. 937–952.e18, 2019.","apa":"Schwayer, C., Shamipour, S., Pranjic-Ferscha, K., Schauer, A., Balda, M., Tada, M., … Heisenberg, C.-P. J. (2019). Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2019.10.006\">https://doi.org/10.1016/j.cell.2019.10.006</a>","mla":"Schwayer, Cornelia, et al. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” <i>Cell</i>, vol. 179, no. 4, Cell Press, 2019, p. 937–952.e18, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.10.006\">10.1016/j.cell.2019.10.006</a>.","ama":"Schwayer C, Shamipour S, Pranjic-Ferscha K, et al. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. <i>Cell</i>. 2019;179(4):937-952.e18. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.10.006\">10.1016/j.cell.2019.10.006</a>","chicago":"Schwayer, Cornelia, Shayan Shamipour, Kornelija Pranjic-Ferscha, Alexandra Schauer, M Balda, M Tada, K Matter, and Carl-Philipp J Heisenberg. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” <i>Cell</i>. Cell Press, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.10.006\">https://doi.org/10.1016/j.cell.2019.10.006</a>.","ista":"Schwayer C, Shamipour S, Pranjic-Ferscha K, Schauer A, Balda M, Tada M, Matter K, Heisenberg C-PJ. 2019. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Cell. 179(4), 937–952.e18.","short":"C. Schwayer, S. Shamipour, K. Pranjic-Ferscha, A. Schauer, M. Balda, M. Tada, K. Matter, C.-P.J. Heisenberg, Cell 179 (2019) 937–952.e18."},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"}],"scopus_import":"1","oa":1,"article_type":"original","day":"31","file":[{"file_name":"2019_Cell_Schwayer_accepted.pdf","file_size":8805878,"file_id":"8684","relation":"main_file","date_updated":"2020-10-21T07:09:45Z","date_created":"2020-10-21T07:09:45Z","content_type":"application/pdf","creator":"dernst","checksum":"33dac4bb77ee630e2666e936b4d57980","success":1,"access_level":"open_access"}],"file_date_updated":"2020-10-21T07:09:45Z","month":"10","ddc":["570"],"oa_version":"Submitted Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_created":"2019-11-12T12:51:06Z","doi":"10.1016/j.cell.2019.10.006","date_updated":"2026-09-12T22:30:22Z","ec_funded":1,"department":[{"_id":"CaHe"},{"_id":"BjHo"}],"type":"journal_article","pmid":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"7186"},{"status":"public","relation":"dissertation_contains","id":"8350"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/biochemistry-meets-mechanics-the-sensitive-nature-of-cell-cell-contact-formation-in-embryo-development/","description":"News auf IST Website"}]},"project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573"}],"page":"937-952.e18","issue":"4","external_id":{"pmid":["31675500"],"isi":["000493898000012"]},"quality_controlled":"1","_id":"7001","article_processing_charge":"No","publisher":"Cell Press","volume":179,"publication":"Cell","status":"public","language":[{"iso":"eng"}],"intvolume":"       179","publication_status":"published","has_accepted_license":"1","year":"2019","isi":1,"title":"Mechanosensation of tight junctions depends on ZO-1 phase separation and flow","author":[{"last_name":"Schwayer","first_name":"Cornelia","orcid":"0000-0001-5130-2226","id":"3436488C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwayer, Cornelia"},{"full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","first_name":"Shayan","last_name":"Shamipour"},{"last_name":"Pranjic-Ferscha","first_name":"Kornelija","id":"4362B3C2-F248-11E8-B48F-1D18A9856A87","full_name":"Pranjic-Ferscha, Kornelija"},{"id":"30A536BA-F248-11E8-B48F-1D18A9856A87","full_name":"Schauer, Alexandra","first_name":"Alexandra","orcid":"0000-0001-7659-9142","last_name":"Schauer"},{"full_name":"Balda, M","last_name":"Balda","first_name":"M"},{"full_name":"Tada, M","first_name":"M","last_name":"Tada"},{"full_name":"Matter, K","last_name":"Matter","first_name":"K"},{"last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"date_published":"2019-10-31T00:00:00Z"},{"article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","_id":"6947","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","language":[{"iso":"eng"}],"status":"public","abstract":[{"lang":"eng","text":"Lymph nodes  are es s ential organs  of the immune  s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular  cells (FRCs) are  the  main  stromal  cells and  form  a sponge-like extracellular matrix network,   called  conduits ,  which  they   thems elves   enwrap   and  contract.  Lymph,  containing  s oluble  antigens ,  arrive in  lymph  nodes  via afferent lymphatic  vessels that  connect  to  the  s ubcaps ular  s inus   and  conduit  network.  According  to  the  current  paradigm,  the  conduit  network   dis tributes   afferent  lymph  through   lymph  nodes   and  thus   provides   acces s   for  immune  cells to lymph-borne  antigens. An  elas tic  caps ule  s urrounds   the  organ  and  confines   the immune  cells and  FRC  network.   Lymph   nodes   are  completely  packed  with  lymphocytes   and  lymphocyte  numbers  directly  dictates  the size  of  the  organ.  Although  lymphocytes   cons tantly  enter  and  leave  the  lymph  node,  its   s ize  remains   remarkedly   s table  under  homeostatic conditions. It is only partly known  how the cellularity and s ize of the lymph node is regulated and  how  the  lymph  node  is able to swell in inflammation.  The role of the FRC network   in  lymph  node   s welling  and  trans fer  of  fluids   are  inves tigated in  this   thes is.  Furthermore,   we  s tudied  what  trafficking  routes   are  us ed  by  cancer  cells   in  lymph  nodes   to  form  distal metastases.We examined the role of a mechanical feedback in regulation of lymph  node swelling. Using parallel plate compression  and UV-las er  cutting  experiments   we  dis s ected  the  mechanical  force dynamics  of the whole lymph  node, and individually for FRCs  and the  caps ule. Physical forces   generated  by  packed  lymphocytes   directly  affect  the  tens ion  on  the  FRC  network  and  capsule,  which  increases  its  resistance  to   swelling.  This  implies  a  feedback  mechanism  between   tis s ue   pres s ure   and   ability   of   lymphocytes    to   enter   the   organ.   Following   inflammation,  the  lymph  node  swells ∼10 fold in two weeks . Yet, what  is  the role  for tens ion on  the  FRC  network   and  caps ule,  and  how  are  lymphocytes   able  to  enter  in  conditions  that resist swelling remain open ques tions . We s how that tens ion on the FRC network is  important to  limit  the  swelling  rate  of  the  organ  so  that  the  FRC  network  can  grow  in  a  coordinated  fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates  and a dis organized FRC network  in the inflamed lymph  node. Growth  of the FRC network  in  turn  is   expected  to  releas e  tens ion  on  thes e  s tructures   and  lowers   the  res is tance  to  swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of  swelling coincides   with  a  thickening  of  the  caps ule,  which  forms   a  thick  res is tant  band  around  the organ and lowers  tens ion on the FRC network  to form a new force equilibrium.The  FRC  and  conduit   network   are  further   believed  to  be  a  privileged  s ite  of  s oluble  information  within  the  lymph  node,  although  many  details   remain  uns olved.  We  s how  by  3D  ultra-recons truction   that  FRCs   and  antigen  pres enting  cells   cover  the  s urface  of  conduit  s ys tem for more  than 99% and we dis cus s  the implications  for s oluble information  exchangeat the conduit level.Finally, there  is an ongoing debate in the cancer field whether and how cancer cells  in lymph nodes   s eed  dis tal  metas tas es .  We  s how  that  cancer  cells   infus ed  into  the  lymph  node  can  utilize trafficking routes of immune  cells and  rapidly  migrate  to  blood  vessels. Once  in  the  blood circulation,  these cells are able to form  metastases in distal tissues."}],"year":"2019","has_accepted_license":"1","publication_status":"published","date_published":"2019-10-09T00:00:00Z","title":"Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking","author":[{"full_name":"Assen, Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119","first_name":"Frank P","last_name":"Assen"}],"OA_place":"publisher","oa":1,"fulldoi":"https://doi.org/10.15479/AT:ISTA:6947","publication_identifier":{"issn":["2663-337X"]},"citation":{"apa":"Assen, F. P. (2019). <i>Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6947\">https://doi.org/10.15479/AT:ISTA:6947</a>","mla":"Assen, Frank P. <i>Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6947\">10.15479/AT:ISTA:6947</a>.","ieee":"F. P. Assen, “Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking,” Institute of Science and Technology Austria, 2019.","ama":"Assen FP. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6947\">10.15479/AT:ISTA:6947</a>","chicago":"Assen, Frank P. “Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6947\">https://doi.org/10.15479/AT:ISTA:6947</a>.","ista":"Assen FP. 2019. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria.","short":"F.P. Assen, Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking, Institute of Science and Technology Austria, 2019."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"supervisor":[{"orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"file_date_updated":"2020-11-07T23:30:03Z","file":[{"access_level":"closed","embargo_to":"open_access","checksum":"53a739752a500f84d0f8ec953cbbd0b6","creator":"fassen","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2020-11-07T23:30:03Z","date_created":"2019-11-06T12:30:02Z","relation":"source_file","file_id":"6990","file_name":"PhDthesis_FrankAssen_revised2.docx","file_size":214172667},{"checksum":"8c156b65d9347bb599623a4b09f15d15","creator":"fassen","content_type":"application/pdf","date_created":"2019-11-06T12:30:57Z","relation":"main_file","date_updated":"2020-11-07T23:30:03Z","file_id":"6991","file_size":83637532,"file_name":"PhDthesis_FrankAssen_revised2.pdf","embargo":"2020-11-06","access_level":"open_access"}],"day":"09","doi":"10.15479/AT:ISTA:6947","date_updated":"2026-06-18T18:47:59Z","date_created":"2019-10-14T16:54:52Z","corr_author":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","oa_version":"Published Version","ddc":["570"],"month":"10","page":"142","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"664"},{"relation":"part_of_dissertation","status":"public","id":"402"}]},"type":"dissertation","department":[{"_id":"MiSi"}]},{"corr_author":"1","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","oa_version":"Published Version","ddc":["570"],"month":"09","date_created":"2019-09-06T06:54:16Z","date_updated":"2026-09-03T06:40:36Z","doi":"10.15479/AT:ISTA:6849","type":"dissertation","department":[{"_id":"JoCs"},{"_id":"GradSch"}],"page":"97","related_material":{"record":[{"id":"5914","relation":"part_of_dissertation","status":"public"}]},"fulldoi":"https://doi.org/10.15479/AT:ISTA:6849","publication_identifier":{"isbn":["978-3-99078-003-9"],"issn":["2663-337X"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"M-Shop"}],"citation":{"apa":"Rangel Guerrero, D. K. (2019). <i>The role of CCK-interneurons in regulating hippocampal network dynamics</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6849\">https://doi.org/10.15479/AT:ISTA:6849</a>","mla":"Rangel Guerrero, Dámaris K. <i>The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6849\">10.15479/AT:ISTA:6849</a>.","ieee":"D. K. Rangel Guerrero, “The role of CCK-interneurons in regulating hippocampal network dynamics,” Institute of Science and Technology Austria, 2019.","ama":"Rangel Guerrero DK. The role of CCK-interneurons in regulating hippocampal network dynamics. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6849\">10.15479/AT:ISTA:6849</a>","short":"D.K. Rangel Guerrero, The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics, Institute of Science and Technology Austria, 2019.","chicago":"Rangel Guerrero, Dámaris K. “The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6849\">https://doi.org/10.15479/AT:ISTA:6849</a>.","ista":"Rangel Guerrero DK. 2019. The role of CCK-interneurons in regulating hippocampal network dynamics. Institute of Science and Technology Austria."},"supervisor":[{"last_name":"Csicsvari","first_name":"Jozsef L","orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L"}],"OA_place":"publisher","oa":1,"day":"09","file_date_updated":"2021-02-10T23:30:09Z","doi_confirm":"1","file":[{"file_id":"6865","file_name":"Thesis_Damaris_Rangel_source.docx","file_size":18253100,"date_created":"2019-09-09T13:09:45Z","relation":"source_file","date_updated":"2021-02-10T23:30:09Z","creator":"drangel","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"244dc4f74dbfc94f414156092298831f","embargo_to":"open_access","access_level":"closed"},{"relation":"main_file","date_created":"2019-09-09T13:09:52Z","date_updated":"2020-09-11T22:30:04Z","embargo":"2020-09-10","file_name":"Thesis_Damaris_Rangel_pdfa.pdf","file_size":2160109,"file_id":"6866","checksum":"59c73be40eeaa1c4db24067270151555","content_type":"application/pdf","creator":"drangel","request_a_copy":0,"access_level":"open_access"}],"year":"2019","has_accepted_license":"1","publication_status":"published","author":[{"id":"4871BCE6-F248-11E8-B48F-1D18A9856A87","full_name":"Rangel Guerrero, Dámaris K","orcid":"0000-0002-8602-4374","first_name":"Dámaris K","last_name":"Rangel Guerrero"}],"title":"The role of CCK-interneurons in regulating hippocampal network dynamics","date_published":"2019-09-09T00:00:00Z","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","_id":"6849","status":"public","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Brain function is mediated by complex dynamical interactions between excitatory and inhibitory cell types. The Cholecystokinin-expressing inhibitory cells (CCK-interneurons) are one of the least studied types, despite being suspected to play important roles in cognitive processes. We studied the network effects of optogenetic silencing of CCK-interneurons in the CA1 hippocampal area during exploration and sleep states. The cell firing pattern in response to light pulses allowed us to classify the recorded neurons in 5 classes, including disinhibited and non-responsive pyramidal cell and interneurons, and the inhibited interneurons corresponding to the CCK group. The light application, which inhibited the activity of CCK interneurons triggered wider changes in the firing dynamics of cells. We observed rate changes (i.e. remapping) of pyramidal cells during the exploration session in which the light was applied relative to the previous control session that was not restricted neither in time nor space to the light delivery. Also, the disinhibited pyramidal cells had higher increase in bursting than in single spike firing rate as a result of CCK silencing. In addition, the firing activity patterns during exploratory periods were more weakly reactivated in sleep for those periods in which CCK-interneuron were silenced than in the unaffected periods. Furthermore, light pulses during sleep disrupted the reactivation of recent waking patterns. Hence, silencing CCK neurons during exploration suppressed the reactivation of waking firing patterns in sleep and CCK interneuron activity was also required during sleep for the normal reactivation of waking patterns. These findings demonstrate the involvement of CCK cells in reactivation-related memory consolidation. An important part of our analysis was to test the relationship of the identified CCKinterneurons to brain oscillations. Our findings showed that these cells exhibited different oscillatory behaviour during anaesthesia and natural waking and sleep conditions. We showed that: 1) Contrary to the past studies performed under anaesthesia, the identified CCKinterneurons fired on the descending portion of the theta phase in waking exploration. 2) CCKinterneuron preferred phases around the trough of gamma oscillations. 3) Contrary to anaesthesia conditions, the average firing rate of the CCK-interneurons increased around the peak activity of the sharp-wave ripple (SWR) events in natural sleep, which is congruent with new reports about their functional connectivity. We also found that light driven CCK-interneuron silencing altered the dynamics on the CA1 network oscillatory activity: 1) Pyramidal cells negatively shifted their preferred theta phases when the light was applied, while interneurons responses were less consistent. 2) As a population, pyramidal cells negatively shifted their preferred activity during gamma oscillations, albeit we did not find gamma modulation differences related to the light application when pyramidal cells were subdivided into the disinhibited and unaffected groups. 3) During the peak of SWR events, all but the CCK-interneurons had a reduction in their relative firing rate change during the light application as compared to the change observed at SWR initiation. Finally, regarding to the place field activity of the recorded pyramidal neurons, we showed that the disinhibited pyramidal cells had reduced place field similarity, coherence and spatial information, but only during the light application. The mechanisms behind such observed behaviours might involve eCB signalling and plastic changes in CCK-interneuron synapses. In conclusion, the observed changes related to the light-mediated silencing of CCKinterneurons have unravelled characteristics of this interneuron subpopulation that might change the understanding not only of their particular network interactions, but also of the current theories about the emergence of certain cognitive processes such as place coding needed for navigation or hippocampus-dependent memory consolidation. "}]}]
