| First Author | Kesavan G | Year | 2014 |
| Journal | Development | Volume | 141 |
| Issue | 3 | Pages | 685-96 |
| PubMed ID | 24449844 | Mgi Jnum | J:208336 |
| Mgi Id | MGI:5562949 | Doi | 10.1242/dev.100297 |
| Citation | Kesavan G, et al. (2014) Cdc42/N-WASP signaling links actin dynamics to pancreatic beta cell delamination and differentiation. Development 141(3):685-96 |
| abstractText | 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 beta cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in beta cells inhibits beta 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 Isl1 and MafA. Mechanistically, we demonstrate that genetic ablation of N-WASP in beta cells expressing constitutively active Cdc42 partially restores both delamination and beta cell differentiation. These findings elucidate how junctional actin dynamics via Cdc42/N-WASP signaling cell-autonomously control not only epithelial delamination but also cell differentiation during mammalian organogenesis. |
