Cdc42/N-WASP signaling links actin dynamics to pancreatic beta cell delamination and differentiation
Research output: Contribution to journal › Journal article › Research › peer-review
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 β 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 β cells inhibits β 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 β cells expressing constitutively active Cdc42 partially restores both delamination and β 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.
Original language | English |
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Journal | Development |
Volume | 141 |
Issue number | 3 |
Pages (from-to) | 685-696 |
Number of pages | 12 |
ISSN | 0950-1991 |
DOIs | |
Publication status | Published - 1 Feb 2014 |
- Beta cell delamination, Differentiation, Cdc42
Research areas
ID: 130760498