Integrin-ECM Interactions Regulate Cadherin-Dependent Cell Adhesion and Are Required for Convergent Extension in Xenopus

AbstractBackground: Convergence extension movements are conserved tissue rearrangements implicated in multiple morphogenetic events. While many of the cell behaviors involved in convergent extension are known, the molecular interactions required for this process remain elusive. However, past evidence suggests that regulation of cell adhesion molecule function is a key step in the progression of these behaviors.Results: Antibody blocking of fibronectin (FN) adhesion or dominant-negative inhibition of integrin β1 function alters cadherin-mediated cell adhesion, promotes cell-sorting behaviors in reaggregation assays, and inhibits medial-lateral cell intercalation and axial extension in gastrulating embryos and explants. Embryo explants were used to demonstrate that normal integrin signaling is required for morphogenetic movements within defined regions but not for cell fate specification. The binding of soluble RGD-containing fragments of fibronectin to integrins promotes the reintegration of dissociated single cells into intact tissues. The changes in adhesion observed are independent of cadherin or integrin expression levels.Conclusions: We conclude that integrin modulation of cadherin adhesion influences cell intercalation behaviors within boundaries defined by extracellular matrix. We propose that this represents a fundamental mechanism promoting localized cell rearrangements throughout development