preprint draft Naoya Hino author 5299a9ce-7679-11eb-a7bc-d1e62b936307 Tushna Kapoor author e3b3eda7-fd4d-11eb-8fd8-c40af7a478b1 Uday R Gubbala author bb4a0dc4-32c9-11ee-b5ce-a97ceedd5924 Edouard B Hannezo author 3A9DB764-F248-11E8-B48F-1D18A9856A870000-0001-6005-1561 Carl-Philipp J Heisenberg author 39427864-F248-11E8-B48F-1D18A9856A870000-0002-0912-4566 CaHe department EdHa department GradSch department Keratins in epithelial tissue spreading project Mechanosensitive signaling activation in the crosstalk between mechanical force and tissuefluidity project 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. https://research-explorer.ista.ac.at/download/22276/22283/Main_text_and_figures.pdf application/pdfno https://research-explorer.ista.ac.at/download/22276/22284/Supplementary_figures.pdf application/pdfno https://research-explorer.ista.ac.at/download/22276/22285/Supplementary_Video1.mp4 video/mp4no Institute of Science and Technology Austria2026 eng Epithelial spreadingtissue tensionmechanosensationaPKCKibrazebrafish https://research-explorer.ista.ac.at/record/21864 Hino, Naoya, et al. <i>Apical Domain Mechanosensation Regulates Tissue Tension Homeostasis</i>. Institute of Science and Technology Austria. Hino N, Kapoor T, Gubbala UR, Hannezo EB, Heisenberg C-PJ. Apical domain mechanosensation regulates tissue tension homeostasis. 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. 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. 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. Hino N, Kapoor T, Gubbala UR, Hannezo EB, Heisenberg C-PJ. Apical domain mechanosensation regulates tissue tension homeostasis. N. Hino, T. Kapoor, U.R. Gubbala, E.B. Hannezo, C.-P.J. Heisenberg, (n.d.). 222762026-07-13T09:03:26Z2026-07-14T07:07:41Z