Cdc42/N-WASP signaling links actin dynamics to pancreatic Î² cell delamination and differentiation.

[wiskott-aldrich syndrome]

Delamination plays a pivotal role during normal development and cancer . Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype . However , how this positional change is linked to differentiation remains unknown . Using the developing mouse pancreas as a model system , we show that Î² cell delamination and differentiation are two independent events , which are controlled by Cdc 42 /N-WASP signaling . Specifically , we show that expression of constitutively active Cdc 42 in Î² cells inhibits Î² cell delamination and differentiation . These processes are normally associated with junctional actin and cell-cell junction disassembly and the expression of fate-determining transcription factors , such as Isl 1 and MafA . Mechanistically , we demonstrate that genetic ablation of N-WASP in Î² cells expressing constitutively active Cdc 42 partially restores both delamination and Î² cell differentiation . These findings elucidate how junctional actin dynamics via Cdc 42 /N-WASP signaling cell-autonomously control not only epithelial delamination but also cell differentiation during mammalian organogenesis .