title: Rho signalling restriction by the RhoGAP Stard13 integrates growth and morphogenesis in the pancreas.
abstract: The development of functional organ architecture relies on coordinated morphogenesis and growth. In the developing pancreas, the branching epithelium is organised in discrete domains, delineating one specific domain of progenitor cells at the tip of the branches. The molecular mechanisms underlying the coordinated action of branching and proliferation in organ formation are largely unknown. Here, we identify the RhoGAP protein Stard13 as an essential regulator of pancreas tissue architecture in the mammalian embryo. Conditional ablation of Stard13 expression in the pancreas disrupts epithelial morphogenesis and tip-domain organisation, resulting in hampered proliferation of tip progenitors and subsequent organ hypoplasia. Stard13 acts by regulating Rho signalling spatially and temporally during pancreas development. Our findings provide new insights into the mechanisms that shape pancreatic epithelium to create a mature organ and establish a functional link between Rho-mediated control of epithelial remodelling and organ size determination, involving reciprocal interaction of actin-MAL/SRF and MAPK signalling pathways.
authors.affiliation: Laboratory of Molecular and Cellular Basis of Embryonic Development, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Petzold
authors.forename: Heike
authors.initials: H
authors.lastname: Naumann
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Spagnoli
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D009924:Organ Culture Techniques; D010179:Pancreas / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D020690:GTPase-Activating Proteins; C473607:STARD13 protein, human; D025521:Tumor Suppressor Proteins; C085379:rho GTPase-activating protein