Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation
| Autor: | Anant Mamidi, Jenny Johansson, Henrik Semb, Zarah Löf Öhlin, Thomas U. Greiner, Gokul Kesavan, Silvia Lommel, Wan Chun Li, Oliver Lieven |
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| Rok vydání: | 2014 |
| Předmět: |
Cellular differentiation
Cell Wiskott-Aldrich Syndrome Protein Neuronal macromolecular substances CDC42 Biology Time-Lapse Imaging Cell junction Epithelium Mice Insulin-Secreting Cells medicine Animals Humans cdc42 GTP-Binding Protein Molecular Biology Transcription factor Research Articles Actin Actin remodeling Cell Differentiation Cell Biology Embryo Mammalian Actins Rats Cell biology Intercellular Junctions medicine.anatomical_structure Animals Newborn Cdc42 GTP-Binding Protein Hyperglycemia ISL1 Signal transduction Signal Transduction Developmental Biology |
| Zdroj: | Development. 141:685-696 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.100297 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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