α-Parvin regulation of cell rearrangement is critical for ureteric bud branching morphogenesis

Abstract

All branched tubular structures, including the kidney collecting system, are formed by branching morphogenesis, a process that includes tip branching and trunk narrowing. Tight control of cell movement and rearrangement is a prerequisite for branching morphogenesis. The role of integrin-associated adhesion proteins in coordinating actin dynamics and cell rearrangement during branching morphogenesis is poorly understood. Here, we used three-dimensional live imaging of mouse ureteric bud branching to show that α-parvin, a component of the integrin binding ILK-PINCH-parvin complex, regulates tip branching and tubule thinning by inhibiting excessive cell adhesion and actin polymerization. Mechanistically, α-parvin promotes actin turnover by inhibiting activation of the small guanosine triphosphatases RhoA and Cdc42, which in turn enhances the severing function of the actin regulatory protein, cofilin. These results underscore the importance of adhesion protein–regulated actin dynamics in the critical process of cell rearrangement, which is required for branching morphogenesis.