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Sidekick2 facilitates multiciliated cell penetration through multicellular adherens junctions

Preprint Created on 06 Jun 2026 bioRxiv

Multicellular vertices are important cellular interfaces for mediating tissue dynamics across the epithelium. Here, we report that expression of the vertebrate adhesion protein, Sidekick2 (Sdk2), localizes to vertebrate multicellular adherens junctions in the embryonic Xenopus laevis epithelium. Using the developmental process of radial intercalation, we find Sdk2 facilitates multiciliated cell penetrance into the outer epithelium at multicellular junctions. With fluorescence recovery after photobleaching, we characterize Sdk2 dynamics at multicellular and bicellular junctions and interrogate how the intracellular and extracellular domains of Sdk2 contribute to these dynamics. We observe that overexpression of the highly conserved C terminal intracellular domain alone but not the extracellular domain alone is sufficient to act as a dominant negative, delaying radial intercalation. These results implicate Sdk2s intracellular interactions as critical for regulating the junctional remodeling required during radial intercalation. Ultimately, our findings implicate Sdk2 as a component of multicellular vertices that aids the governance of epithelial integrity.

Suva, E., Higashi, T., Mitchell, B.

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