Expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins in the developing pancreas: Roles in the adhesion and migration of putative endocrine progenitor cells

Cell-cell and cell-matrix, interactions play a critical role in tissue morp hogenesis and in homeostasis of adult tissues. The integrin family of adhes ion receptors regulates cellular interactions with the extracellular matrix , which provides three-dimensional information for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentia ted progenitors residing within the ductal epithelium of the fetal pancreas . This process involves cell budding from the duct, migration into the surr ounding mesenchyme, differentiation, and clustering into the highly organiz ed islet of Langerhans. Here we report that alpha(v)beta(3) and alpha(v)bet a(5), two integrins known to coordinate epithelial cell adhesion and moveme nt, are expressed in pancreatic ductal cells and clusters of undifferentiat ed cells emerging from the ductal epithelium. We show that expression and f unction of alpha(v)beta(3) and alpha(v)beta(5) integrins are developmentall y regulated during pancreatic islet ontogeny, and mediate adhesion and migr ation of putative endocrine progenitor cells both in vitro and in vivo in a model of pancreatic islet development. Moreover, we demonstrate the expres sion of fibronectin and collagen IV in the basal membrane of pancreatic duc ts and of cell clusters budding from the ductal epithelium. Conversely, exp ression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancreatic ducts. Thus, these data provide the first evid ence for the contribution of integrins alpha(v)beta(3) and alpha(v)beta(5) and their ligands to morphogenetic events in the human endocrine pancreas.