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Development. 2014 Feb;141(3):685-96. doi: 10.1242/dev.100297.

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

Author information

1
Stem Cell Center, Department of Laboratory Medicine, Lund University, BMC B10 Klinikgatan 26, SE-22184 Lund, Sweden.

Abstract

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.

KEYWORDS:

Beta cell delamination; Cdc42; Differentiation

PMID:
24449844
PMCID:
PMC3899820
DOI:
10.1242/dev.100297
[Indexed for MEDLINE]
Free PMC Article
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