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Recent evidences suggested that growth and differentiation of pancreatic cell lineages, including the insulin-producing β-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, Stard13RhoGAP, 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.
Descot,
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
2009, Pubmed
Descot,
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
2009,
Pubmed Etienne-Manneville,
Rho GTPases in cell biology.
2002,
Pubmed Ferby,
Mig6 is a negative regulator of EGF receptor-mediated skin morphogenesis and tumor formation.
2006,
Pubmed Fuchs,
Socializing with the neighbors: stem cells and their niche.
2004,
Pubmed Glotzer,
Animal cell cytokinesis.
2001,
Pubmed Greiner,
Rac1 regulates pancreatic islet morphogenesis.
2009,
Pubmed Hick,
Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1.
2009,
Pubmed Hogan,
Organogenesis: molecular mechanisms of tubulogenesis.
2002,
Pubmed Horb,
Role of cell division in branching morphogenesis and differentiation of the embryonic pancreas.
2000,
Pubmed Kesavan,
Cdc42-mediated tubulogenesis controls cell specification.
2009,
Pubmed Michael,
Pattern and regulation of cell proliferation during murine ureteric bud development.
2004,
Pubmed Moore,
Control of basement membrane remodeling and epithelial branching morphogenesis in embryonic lung by Rho and cytoskeletal tension.
2005,
Pubmed Morin,
Mitotic spindle orientation in asymmetric and symmetric cell divisions during animal development.
2011,
Pubmed Morin,
Constitutively active RhoA inhibits proliferation by retarding G(1) to S phase cell cycle progression and impairing cytokinesis.
2009,
Pubmed Nelson,
Emergent patterns of growth controlled by multicellular form and mechanics.
2005,
Pubmed Nelson,
Geometric control of tissue morphogenesis.
2009,
Pubmed Nogawa,
Bud formation precedes the appearance of differential cell proliferation during branching morphogenesis of mouse lung epithelium in vitro.
1998,
Pubmed Pan,
Pancreas organogenesis: from bud to plexus to gland.
2011,
Pubmed Petzold,
Rho signalling restriction by the RhoGAP Stard13 integrates growth and morphogenesis in the pancreas.
2013,
Pubmed
,
Xenbase Petzold,
A system for ex vivo culturing of embryonic pancreas.
2012,
Pubmed
,
Xenbase Piekny,
Cytokinesis: welcome to the Rho zone.
2005,
Pubmed Posern,
Actin' together: serum response factor, its cofactors and the link to signal transduction.
2006,
Pubmed Puri,
Cellular plasticity within the pancreas--lessons learned from development.
2010,
Pubmed Rawlins,
The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells.
2009,
Pubmed Roszko,
Key role played by RhoA in the balance between planar and apico-basal cell divisions in the chick neuroepithelium.
2006,
Pubmed Sordella,
Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis.
2003,
Pubmed Spagnoli,
From endoderm to pancreas: a multistep journey.
2007,
Pubmed
,
Xenbase Stanger,
Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver.
2007,
Pubmed Tcherkezian,
Current knowledge of the large RhoGAP family of proteins.
2007,
Pubmed Van Aelst,
Role of Rho family GTPases in epithelial morphogenesis.
2002,
Pubmed Vartiainen,
Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL.
2007,
Pubmed Villasenor,
Epithelial dynamics of pancreatic branching morphogenesis.
2010,
Pubmed
,
Xenbase Zallen,
Multicellular dynamics during epithelial elongation.
2008,
Pubmed Zhou,
A multipotent progenitor domain guides pancreatic organogenesis.
2007,
Pubmed
