title: ECM Signaling Regulates Collective Cellular Dynamics to Control Pancreas Branching Morphogenesis.
abstract: During pancreas development, epithelial buds undergo branching morphogenesis to form an exocrine and endocrine gland. Proper morphogenesis is necessary for correct lineage allocation of pancreatic progenitors; however, the cellular events underlying pancreas morphogenesis are unknown. Here, we employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. We observed that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; additionally, they largely remain in the outer cell compartment even after mitosis. These cell behaviors and pancreas branching depend on cell contacts with the basement membrane, which induce actomyosin cytoskeleton remodeling via integrin-mediated activation of FAK/Src signaling. We show that integrin signaling reduces E-cadherin-mediated cell-cell adhesion in outer cells and provide genetic evidence that this regulation is necessary for initiation of branching. Our study suggests that regulation of cell motility and adhesion by local niche cues initiates pancreas branching morphogenesis.
authors.affiliation: Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Hung Ping
authors.initials: HP
authors.lastname: Shih
authors.affiliation: Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Panlasigui
authors.affiliation: Department of Medicine, Diabetes and Obesity Center of Excellence, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98105, USA.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cirulli
authors.affiliation: Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: masander@ucsd.edu.
authors.forename: Maike
authors.initials: M
authors.lastname: Sander
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation; D009024:Morphogenesis; D010179:Pancreas / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015820:Cadherins
keywords: E-cadherin; FAK; Src; adhesion; branching; extracellular matrix; integrin; morphogenesis; pancreas; progenitor; time-lapse imaging