@misc{21137,
  author       = {Naik, Suyash},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Data associated with Keratins coordinate tissue spreading }},
  doi          = {10.15479/AT-ISTA-21137},
  year         = {2026},
}

@unpublished{22276,
  abstract     = {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.},
  author       = {Hino, Naoya and Kapoor, Tushna and Gubbala, Uday R and Hannezo, Edouard B and Heisenberg, Carl-Philipp J},
  keywords     = {Epithelial spreading, tissue tension, mechanosensation, aPKC, Kibra, zebrafish},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Apical domain mechanosensation regulates tissue tension homeostasis}},
  year         = {2026},
}

@phdthesis{20441,
  abstract     = {Epithelial spreading plays a pivotal role in the development of organisms especially those
such as zebrafish which require the epithelial enveloping layer (EVL) to spread to cover the
substantial yolk surface during gastrulation. Epiboly requires the transition of the epithelium
with cuboidal cells to form a thin, flat squamous epithelial sheet. During this transition, the
cells show tissue-scale mechanosensation with mechanisms such as direct mechanical control
over the axis of cell division.
Cytoskeletal intermediate filaments play a crucial role in vertebrate cells, not only facilitating
mechanical stability but also helping facilitate the mechanosensitive response of the cell.
Mechanosenstivity displayed by intermediate filaments is due not just to their interesting
physical properties but also to their interactions with other cytoskeletal elements such as actin
and microtubules. Keratin is the predominant intermediate filament expressed in the EVL.
It expresses concomitantly with the gastrulation movements of the developing embryo. Our
work focuses on understanding the role and dynamics of the keratin cytoskeletal network in
modulating the physical aspects of EVL spreading. We demonstrated with the combination of
physical characterisation and manipulations of the EVL, utilising a variety of biophysical tools
and microscopy, the mechanistic role of keratin in tissue spreading.
Generating novel genetic morphants and mutants, we probe the effect that the loss of the
keratin network has on the physiology of the epithelium and the developing embryo. We
show that the changing organisation of the keratin network is important for changing EVL
physical properties as the stress imposed on the EVL increases during epiboly. By modelling
the epithelium, we study how the mechanical heterogeneity in an epithelium can feed back into
a mechanical loop to the maturation of the keratin network and hence affect the mechanics
of the epithelium. However, unlike what would be predicted by the effect of intermediate
filaments in acting as a security belt and increasing the resistance of the epithelium, we observe
that loss of keratin leads to a delay in the EVL movement. Using both local aspirations of the
YSL and EVL ablations, we demonstrate the mechanistic facilitation of actin mechanosensation
in a keratin-dependent manner.
Furthermore, using chemical inhibitors of microtubule polymerisation, we provide insight into
the mechanisms underlying the organisation and distribution of keratin. Interestingly, the
phenotype observed upon this loss of microtubules shows that keratins interact with the nucleus
through microtubular interactions. Together with these diverse observations, we describe
the mechanosensory feedback between resilience and that is critical for uniform and robust
spreading of the epithelium.},
  author       = {Naik, Suyash},
  isbn         = {978-3-99078-069-5},
  issn         = {2663-337X},
  pages        = {105},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Keratins act as global coordinators of tissue spreading through mechanosensitive feedback}},
  doi          = {10.15479/AT-ISTA-20441},
  year         = {2025},
}