[{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"22276","has_accepted_license":"1","date_published":"2026-07-14T00:00:00Z","type":"preprint","oa_version":"Preprint","month":"07","publication_status":"draft","abstract":[{"lang":"eng","text":"Tissue tension is a key determinant of tissue shape, and its regulation is essential for both morphogenesis and the maintenance of tissue integrity. During zebrafish embryogenesis, the enveloping layer (EVL) – an epithelial monolayer covering the blastoderm – undergoes extensive spreading that is driven by pulling forces exerted at its margin and more than doubles its surface area. Yet whether and how the EVL actively regulates its tissue tension during this process remains unclear. Here, we show that the EVL maintains constant tissue tension while spreading, and that it achieves this by reducing apical cell contractility in response to the same pulling forces that drive its spreading. We identify a mechanosensitive pathway underlying this response, mediated by the scaffold/adaptor protein Kibra regulating the activity of atypical protein kinase C (aPKC) at the apical domain of EVL cells. Under low mechanical stretch, Kibra forms condensates at the base of actin-based apical projections, where it activates Myosin II to increase apical contractility through aPKC downregulation. As mechanical stretch increases, apical projections disassemble, Kibra condensates dissolve, and aPKC activity rises. Elevated aPKC activity in turn reduces apical contractility by reducing Myosin II activity, thereby maintaining constant tissue tension despite increased mechanical stretch. Together, these findings reveal a mechanosensitive mechanism that enables robust adaptation of tissue tension to changing mechanical stretch, ensuring efficient tissue spreading and morphogenesis."}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"author":[{"full_name":"Hino, Naoya","id":"5299a9ce-7679-11eb-a7bc-d1e62b936307","first_name":"Naoya","last_name":"Hino"},{"last_name":"Kapoor","first_name":"Tushna","id":"e3b3eda7-fd4d-11eb-8fd8-c40af7a478b1","full_name":"Kapoor, Tushna"},{"last_name":"Gubbala","first_name":"Uday R","id":"bb4a0dc4-32c9-11ee-b5ce-a97ceedd5924","full_name":"Gubbala, Uday R"},{"orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","last_name":"Hannezo","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"}],"oa":1,"keyword":["Epithelial spreading","tissue tension","mechanosensation","aPKC","Kibra","zebrafish"],"acknowledgement":"We thank all members of the Heisenberg group for discussion and feedback on the manuscript, and the Imaging and Optics Facility, the Life Science Support Facility and the Electron Microscopy Facility of the Institute of Science and Technology Austria (ISTA) for their continued support. We are grateful to M. Sonawane (Tata Institute of Fundamental Research, India) for providing the pCS2-HA-aPKC (PKCι)-V260F (DN) and pCS2-HA-aPKC (PKCι)-A122E (CA) plasmids, and to I. Mayer for the discussion. Molecular graphics and analyses were performed with UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases. This research was funded in whole or in part by the Austrian Science Fund (FWF; grant no. PAT5044023) to C.-P.H., and by a JSPS Overseas Research Fellowship and an EMBO Postdoctoral Fellowship (ALTF 16-2022) to N.H.","year":"2026","article_processing_charge":"No","day":"14","related_material":{"record":[{"status":"public","relation":"earlier_version","id":"21864"}]},"language":[{"iso":"eng"}],"ddc":["570"],"publisher":"Institute of Science and Technology Austria","date_created":"2026-07-13T09:03:26Z","supplementarymaterial":"yes","OA_type":"green","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"status":"public","date_updated":"2026-07-14T07:07:41Z","title":"Apical domain mechanosensation regulates tissue tension homeostasis","file_date_updated":"2026-07-13T09:16:28Z","dataavailabilitystatement":"The MATLAB code for image analysis, and the full model code, including all parameter values\r\nand condition-specific settings, are available on GitHub at https://github.com/uday2607/EVL-tension-homeostasis.git.","das_tickbox":"1","citation":{"ieee":"N. Hino, T. Kapoor, U. R. Gubbala, E. B. Hannezo, and C.-P. J. Heisenberg, “Apical domain mechanosensation regulates tissue tension homeostasis.” Institute of Science and Technology Austria.","ista":"Hino N, Kapoor T, Gubbala UR, Hannezo EB, Heisenberg C-PJ. Apical domain mechanosensation regulates tissue tension homeostasis.","chicago":"Hino, Naoya, Tushna Kapoor, Uday R Gubbala, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Apical Domain Mechanosensation Regulates Tissue Tension Homeostasis.” Institute of Science and Technology Austria, n.d.","short":"N. Hino, T. Kapoor, U.R. Gubbala, E.B. Hannezo, C.-P.J. Heisenberg, (n.d.).","mla":"Hino, Naoya, et al. <i>Apical Domain Mechanosensation Regulates Tissue Tension Homeostasis</i>. Institute of Science and Technology Austria.","ama":"Hino N, Kapoor T, Gubbala UR, Hannezo EB, Heisenberg C-PJ. Apical domain mechanosensation regulates tissue tension homeostasis.","apa":"Hino, N., Kapoor, T., Gubbala, U. R., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (n.d.). Apical domain mechanosensation regulates tissue tension homeostasis. Institute of Science and Technology Austria."},"project":[{"_id":"8f060199-16d5-11f0-9cad-f3253b266c46","name":"Keratins in epithelial tissue spreading","grant_number":"PAT 5044023"},{"_id":"34dd7f3b-11ca-11ed-8bc3-856f2c87f5da","grant_number":"LTF 16-2022","name":"Mechanosensitive signaling activation in the crosstalk between mechanical force and tissuefluidity"}],"department":[{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"GradSch"}],"OA_place":"publisher","file":[{"date_created":"2026-07-13T09:16:20Z","relation":"main_file","checksum":"66444afd243dce7d383d52d44e8d34a4","file_name":"Main_text_and_figures.pdf","file_id":"22283","file_size":12477675,"content_type":"application/pdf","success":1,"access_level":"open_access","creator":"nhino","date_updated":"2026-07-13T09:16:20Z"},{"date_updated":"2026-07-13T09:16:25Z","content_type":"application/pdf","success":1,"creator":"nhino","access_level":"open_access","file_name":"Supplementary_figures.pdf","file_size":4545901,"file_id":"22284","date_created":"2026-07-13T09:16:25Z","relation":"main_file","checksum":"90bceb34de64ec792c5de117f0890d05"},{"checksum":"9d9ab89c372142f2ffb6c8c625334d7f","relation":"main_file","date_created":"2026-07-13T09:16:28Z","file_id":"22285","file_size":10349451,"file_name":"Supplementary_Video1.mp4","access_level":"open_access","creator":"nhino","success":1,"content_type":"video/mp4","date_updated":"2026-07-13T09:16:28Z"}],"researchdata_availability":"yes","corr_author":"1"}]