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

• DOI: 10.1101/2023.07.14.549074
• Publication Date: 2023-07-16T05:30:18Z
• Authors: Nadia M.E. Ayad; Johnathon N. Lakins; Ajinkya Ghagre; Allen J. Ehrlicher; Valerie M. Weaver
• Keywords: Brachyury; Beta-catenin; Cell fate determination

The role of morphogenetic forces in cell fate specification is an area intense interest. Our prior studies suggested that the development high cell-cell tension human embryonic stem cells (hESC) colonies permits Src-mediated phosphorylation junctional β-catenin accelerates its release to potentiate Wnt-dependent signaling critical for initiating mesoderm specification. Using ectopically expressed nonphosphorylatable mutant (Y654F), we now provide direct evidence impeding tension-dependent impedes expression Brachyury (T) and epithelial-to-mesenchymal transition (EMT) necessary Addition exogenous Wnt3a or inhibiting GSK3β activity rescued expression, emphasizing importance force dependent Wnt regulating mechanomorphogenesis. work provides a framework understanding β-catenin/Wnt self-organization tissues during developmental processes including gastrulation.