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RhoGAP control of pancreas development: putting cells in the right place at the right time

Item Type:Comment
Title:RhoGAP control of pancreas development: putting cells in the right place at the right time
Creators Name:Zygmunt, T. and Spagnoli, F.M.
Abstract:Recent evidences suggested that growth and differentiation of pancreatic cell lineages, including the insulin-producing {beta}-cells, depend on proper tissue-architecture, epithelial remodeling and cell positioning within the branching pancreatic epithelium. We recently found that Rho GTPase and its regulator, Stard13 RhoGAP, coordinate morphogenesis with growth in the developing pancreas. Conditional mutation of Stard13 in the mouse pancreas hampers epithelial remodeling and distal tip domain formation, affecting proliferation and expansion of pancreatic progenitors. These defects eventually result in pancreatic hypoplasia at birth. Stard13 acts by regulating Rho signaling spatially and temporally during pancreas development. In line with this, pharmacological activation or inhibition of Rho mimics or rescues, respectively, the defects observed in Stard13-deficient embryos and pancreatic organ cultures. Furthermore, in the absence of Stard13 uninhibited Rho activity affects the actomyosin contractile network, disrupting its apical distribution and hampering coordinated cell-shape changes. These results unveil therefore the crucial role of actin cytoskeletal dynamics during the onset of pancreatic branching morphogenesis. Finally, our findings define a reciprocal interaction between the actin-MAL/SRF and the MAPK signaling to locally regulate progenitor cell proliferation in the pancreas.
Keywords:Actin, Branching Morphogenesis, Cytoskeleton, MAPK, Pancreas Development, Progenitor Cells, Rho GTPase, RhoGAP, Stard13, Animals
Source:Small GTPases
Publisher:Landes Bioscience
Page Range:127-131
Date:April 2013
Additional Information:Comment on Development 140(1): 126-135
Official Publication:https://doi.org/10.4161/sgtp.24261
PubMed:View item in PubMed

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