{"page":"105","file":[{"file_size":6846189,"date_updated":"2025-10-28T13:10:08Z","date_created":"2025-10-28T13:10:08Z","relation":"main_file","file_name":"Thesis_PDFA_.pdf","content_type":"application/pdf","creator":"snaik","access_level":"open_access","success":1,"file_id":"20567","checksum":"2892f04d4a5c18677871c3e06ac1244a"},{"relation":"source_file","date_created":"2025-10-28T13:10:26Z","file_size":8839300,"date_updated":"2025-10-28T13:10:26Z","content_type":"application/zip","file_name":"Thesis.zip","access_level":"open_access","creator":"snaik","file_id":"20568","checksum":"15934d4465cd0e9b7c32678da9a33a2f"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"20465"}]},"license":"https://creativecommons.org/licenses/by-sa/4.0/","month":"10","department":[{"_id":"GradSch"},{"_id":"CaHe"},{"_id":"EdHa"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"has_accepted_license":"1","year":"2025","citation":{"chicago":"Naik, Suyash. “Keratins Act as Global Coordinators of Tissue Spreading through Mechanosensitive Feedback.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20441\">https://doi.org/10.15479/AT-ISTA-20441</a>.","apa":"Naik, S. (2025). <i>Keratins act as global coordinators of tissue spreading through mechanosensitive feedback</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20441\">https://doi.org/10.15479/AT-ISTA-20441</a>","mla":"Naik, Suyash. <i>Keratins Act as Global Coordinators of Tissue Spreading through Mechanosensitive Feedback</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20441\">10.15479/AT-ISTA-20441</a>.","ama":"Naik S. Keratins act as global coordinators of tissue spreading through mechanosensitive feedback. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20441\">10.15479/AT-ISTA-20441</a>","short":"S. Naik, Keratins Act as Global Coordinators of Tissue Spreading through Mechanosensitive Feedback, Institute of Science and Technology Austria, 2025.","ieee":"S. Naik, “Keratins act as global coordinators of tissue spreading through mechanosensitive feedback,” Institute of Science and Technology Austria, 2025.","ista":"Naik S. 2025. Keratins act as global coordinators of tissue spreading through mechanosensitive feedback. Institute of Science and Technology Austria."},"ddc":["596","597","532"],"status":"public","language":[{"iso":"eng"}],"oa":1,"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"author":[{"first_name":"Suyash","full_name":"Naik, Suyash","orcid":"0000-0001-8421-5508","last_name":"Naik","id":"2C0B105C-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"text":"Epithelial spreading plays a pivotal role in the development of organisms especially those\r\nsuch as zebrafish which require the epithelial enveloping layer (EVL) to spread to cover the\r\nsubstantial yolk surface during gastrulation. Epiboly requires the transition of the epithelium\r\nwith cuboidal cells to form a thin, flat squamous epithelial sheet. During this transition, the\r\ncells show tissue-scale mechanosensation with mechanisms such as direct mechanical control\r\nover the axis of cell division.\r\nCytoskeletal intermediate filaments play a crucial role in vertebrate cells, not only facilitating\r\nmechanical stability but also helping facilitate the mechanosensitive response of the cell.\r\nMechanosenstivity displayed by intermediate filaments is due not just to their interesting\r\nphysical properties but also to their interactions with other cytoskeletal elements such as actin\r\nand microtubules. Keratin is the predominant intermediate filament expressed in the EVL.\r\nIt expresses concomitantly with the gastrulation movements of the developing embryo. Our\r\nwork focuses on understanding the role and dynamics of the keratin cytoskeletal network in\r\nmodulating the physical aspects of EVL spreading. We demonstrated with the combination of\r\nphysical characterisation and manipulations of the EVL, utilising a variety of biophysical tools\r\nand microscopy, the mechanistic role of keratin in tissue spreading.\r\nGenerating novel genetic morphants and mutants, we probe the effect that the loss of the\r\nkeratin network has on the physiology of the epithelium and the developing embryo. We\r\nshow that the changing organisation of the keratin network is important for changing EVL\r\nphysical properties as the stress imposed on the EVL increases during epiboly. By modelling\r\nthe epithelium, we study how the mechanical heterogeneity in an epithelium can feed back into\r\na mechanical loop to the maturation of the keratin network and hence affect the mechanics\r\nof the epithelium. However, unlike what would be predicted by the effect of intermediate\r\nfilaments in acting as a security belt and increasing the resistance of the epithelium, we observe\r\nthat loss of keratin leads to a delay in the EVL movement. Using both local aspirations of the\r\nYSL and EVL ablations, we demonstrate the mechanistic facilitation of actin mechanosensation\r\nin a keratin-dependent manner.\r\nFurthermore, using chemical inhibitors of microtubule polymerisation, we provide insight into\r\nthe mechanisms underlying the organisation and distribution of keratin. Interestingly, the\r\nphenotype observed upon this loss of microtubules shows that keratins interact with the nucleus\r\nthrough microtubular interactions. Together with these diverse observations, we describe\r\nthe mechanosensory feedback between resilience and that is critical for uniform and robust\r\nspreading of the epithelium.","lang":"eng"}],"supervisor":[{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J"},{"orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","first_name":"Edouard B"}],"title":"Keratins act as global coordinators of tissue spreading through mechanosensitive feedback","date_updated":"2025-11-06T13:56:09Z","corr_author":"1","doi":"10.15479/AT-ISTA-20441","OA_place":"repository","article_processing_charge":"No","_id":"20441","date_published":"2025-10-12T00:00:00Z","date_created":"2025-10-10T14:58:30Z","type":"dissertation","degree_awarded":"PhD","day":"12","acknowledgement":"I would also like to thank the LSF and Cryo facility at ISTA, which have been helpful in my\r\nexperiments. I would also like to acknowledge FWF, grant DOI 10.55776/PAT5044023 and JKU Nanocell grant DOI \r\n10.55776/W1250 for providing funding for my PhD research. EMBO and FWF for providing funding for travel grants to attend conferences.","publisher":"Institute of Science and Technology Austria","tmp":{"short":"CC BY-SA (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","image":"/images/cc_by_sa.png","name":"Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0)"},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","publication_status":"published","project":[{"name":"Keratins in epithelial tissue spreading","grant_number":"PAT 5044023","_id":"8f060199-16d5-11f0-9cad-f3253b266c46"},{"_id":"25AA5F24-B435-11E9-9278-68D0E5697425","name":"Nano-Analytics of Cellular Systems","call_identifier":"FWF","grant_number":"W 1250-B20"}],"file_date_updated":"2025-10-28T13:10:26Z","publication_identifier":{"isbn":["978-3-99078-069-5"],"issn":["2663-337X"]}}