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bioRxiv · 10.64898/2026.05.06.723156

Junctional β-Catenin Stabilization Links Wnt Signaling and Force Generation

Otgonbaatar, A.·Shankar, S.·Kaur, P.·Tawari, P.·Tolwinski, N. S.
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Abstract

{beta}-catenin plays two fundamental roles in animal tissues: it acts as a transcriptional effector of canonical Wnt signaling and as a core structural component of adherens junctions that mediate cell-cell adhesion. In canonical Wnt signaling, the post-transcriptional regulation of {beta}-catenin abundance, primarily through regulated phosphorylation, ubiquitination, and proteasomal degradation, determines whether the pathway is "off" or "on." Despite the central importance of {beta}-catenin stabilization, in vivo measurements of {beta}-catenin protein lifetime and stabilization dynamics during development remain limited. Here, we measure the stability of endogenous {beta}-catenin in vivo using tandem fluorescent protein timers (tFPs; "Timers") inserted as minimally disruptive cassettes within the endogenous locus. Timers allow simultaneous visualization of a newly synthesized, rapidly accumulating pool (fast-maturing GFP) and a long-lived, stabilized pool (slow-maturing RFP). Surprisingly, the strongest stabilization does not occur in canonical Wnt patterning stripes; instead, we observe marked stabilization of junctional {beta}-catenin at the leading edge during dorsal closure, a force-generating morphogenetic process. This stabilization is not explained by canonical Wnt ligand input and seems to reflect a stability program linked to {beta}-catenins adhesive function in adherens junctions. We suggest that a stable junctional pool of {beta}-catenin is vital for dorsal closure mechanics and provide evidence that this stabilization is regulated by Dishevelled and JNK, thus connecting Wnt pathway components to mechanotransduction.

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Otgonbaatar, A., Shankar, S., Kaur, P., Tawari, P., Tolwinski, N. S.. 2026-05-09. Junctional β-Catenin Stabilization Links Wnt Signaling and Force Generation. https://doi.org/10.64898/2026.05.06.723156

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