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

Summary, in English

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.

• Author: Gokul Kesavan; Oliver Lieven; Anant Mamidi; Zarah Löf-Öhlin; Jenny Johansson; Wan-Chun Li; Silvia Lommel; Thomas Greiner; Henrik Semb
• Department/s: Stem Cell Center; EXODIAB: Excellence of Diabetes Research in Sweden
• Publishing year: 2014
• Language: English
• Pages: 685-696
• Publication/Series: Development: For advances in developmental biology and stem cells
• Volume: 141
• Issue: 3
• Links: http://www.ncbi.nlm.nih.gov/pubmed/24449844?dopt=Abstract; http://dx.doi.org/10.1242/dev.100297
• Document type: Journal article
• Publisher: The Company of Biologists Ltd
• Topic: Developmental Biology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1477-9129