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Classical cadherins are well-known adhesion molecules responsible for physically connecting neighboring cells and signaling this cell–cell contact. Recent studies have suggested novel signaling roles for “non-junctional” cadherins (NJCads); however, the function of cadherin signaling independent of cell–cell contacts remains unknown. In this study, mesendodermal cells and tissues from gastrula stageXenopus laevisembryos demonstrate that deletion of extracellular domains of Cadherin3 (Cdh3; formerly C-cadherin inXenopus) disrupts contact inhibition of locomotion. In both bulk Rac1 activity assays and spatio-temporal FRET image analysis, the extracellular and cytoplasmic Cdh3 domains disrupt NJCad signaling and regulate Rac1 activity in opposing directions. Stabilization of the cytoskeleton counteracted this regulation in single cell migration assays. Our study provides novel insights into adhesion-independent signaling by Cadherin3 and its role in regulating single and collective cell migration.

We exist in a physical world, and cells within biological tissues must respond appropriately to both environmental forces and forces generated within the tissue to ensure normal development and homeostasis. Cell division is required for normal tissue growth and maintenance, but both the direction and rate of cell division must be tightly controlled to avoid diseases of over‐proliferation such as cancer. Recent studies have shown that mechanical cues can cause mitotic entry and orient the mitotic spindle, suggesting that physical force could play a role in patterning tissue growth. However, to fully understand how mechanics guides cellsin vivo, it is necessary to assess the interaction of mechanical strain and cell division in a whole tissue context. In this mini‐review we first summarise the body of work linking mechanics and cell division, before looking at the advantages that theXenopusembryo can offer as a model organism for understanding: (1) the mechanical environment during embryogenesis, and (2) factors important for cell division. Finally, we introduce a novel method for applying a reproducible strain toXenopusembryonic tissue and assessing subsequent cell divisions.