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bioRxiv · 10.1101/2023.07.14.549074

Tissue tension permits β-catenin phosphorylation to drive mesoderm specification in human embryonic stem cells.

Ayad, N. M. E.·Lakins, J. N.·Ghagre, A.·Ehrlicher, A. J.·Weaver, V. M.
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Abstract

The role of morphogenetic forces in cell fate specification is an area of intense interest. Our prior studies suggested that the development of high cell-cell tension in human embryonic stem cells (hESC) colonies permits the Src-mediated phosphorylation of junctional {beta}-catenin that accelerates its release to potentiate Wnt-dependent signaling critical for initiating mesoderm specification. Using an ectopically expressed nonphosphorylatable mutant of {beta}-catenin (Y654F), we now provide direct evidence that impeding tension-dependent Src-mediated {beta}-catenin phosphorylation impedes the expression of Brachyury (T) and the epithelial-to-mesenchymal transition (EMT) necessary for mesoderm specification. Addition of exogenous Wnt3a or inhibiting GSK3{beta} activity rescued mesoderm expression, emphasizing the importance of force dependent Wnt signaling in regulating mechanomorphogenesis. Our work provides a framework for understanding tension-dependent {beta}-catenin/Wnt signaling in the self-organization of tissues during developmental processes including gastrulation.

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Ayad, N. M. E., Lakins, J. N., Ghagre, A., Ehrlicher, A. J., Weaver, V. M.. 2023-07-15. Tissue tension permits β-catenin phosphorylation to drive mesoderm specification in human embryonic stem cells.. https://doi.org/10.1101/2023.07.14.549074

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