 The Rockefeller University Press, 0021-9525/2000/09/1445/15 $5.00 The Journal of Cell Biology, Volume 150, Number 6, September 18, 2000 1445–1459 http://www.jcb.org 1445 Expression and Function of  v  3 and  v  5 Integrins in the Developing Pancreas: Roles in the Adhesion and Migration of Putative Endocrine Progenitor Cells Vincenzo Cirulli,* Gillian M. Beattie,* George Klier,  Mark Ellisman, ‡ Camillo Ricordi, § Vito Quaranta,  Francine Frasier,  Jennifer K. Ishii, ¶ Alberto Hayek,* and Daniel R. Salomon ¶ *The Islet Research Laboratory at The Whittier Institute for Diabetes, Department of Pediatrics, and ‡ The National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, California 92037; § The Diabetes Research Institute, University of Miami School of Medicine, Miami, Florida 33136; the  Department of Cell Biology, and the ¶ Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037 Abstract. Cell–cell and cell–matrix interactions play a critical role in tissue morphogenesis and in homeostasis of adult tissues. The integrin family of adhesion recep- tors regulates cellular interactions with the extracellu- lar matrix, which provides three-dimensional informa- tion for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentiated pro- genitors residing within the ductal epithelium of the fe- tal pancreas. This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans. Here we report that  v  3 and  v  5 , two integrins known to coordinate epithelial cell adhe- sion and movement, are expressed in pancreatic ductal cells and clusters of undifferentiated cells emerging from the ductal epithelium. We show that expression and function of  v  3 and  v  5 integrins are develop- mentally regulated during pancreatic islet ontogeny, and mediate adhesion and migration of putative endo- crine progenitor cells both in vitro and in vivo in a model of pancreatic islet development. Moreover, we demonstrate the expression of fibronectin and collagen IV in the basal membrane of pancreatic ducts and of cell clusters budding from the ductal epithelium. Con- versely, expression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancre- atic ducts. Thus, these data provide the first evidence for the contribution of integrins  v  3 and  v  5 and their ligands to morphogenetic events in the human endo- crine pancreas. Key words: pancreatic islets • endocrine progenitors •  v  3 • integrins • cell migration Introduction Interactions of cells with their environment play a critical role in directing embryonic development and in maintain- ing tissue integrity in adult life. The structure/function par- adigm dictates that the architectural elements that deter- mine tissue structure also affect tissue function. In this context, the integrin family of adhesion receptors regu- lates many of the cellular interactions with the extracellu- lar matrix (ECM), 1 which provide critical elements of three-dimensional information for tissue organization. In- tegrins are remarkably multifunctional since they mediate not only adherence to specific ECM proteins, but also reg- ulate the migration and spatial segregation of different cell types within tissues (Hynes, 1987; Sonnenberg, 1993; Gull- berg and Ekblom, 1995), cell proliferation (Schwartz and Ingber, 1994), establishment and maintenance of cytodif- ferentiation (Walker et al., 1989; Strange et al., 1992; Tal- houk et al., 1992; Lin and Bissell, 1993), cell polarity (Jones and Watt, 1993; Watt and Jones, 1993; DiPersio et al., 1997), and ultimately cell survival (Giancotti, 1997). A distinctive feature of developing epithelia is the cell type–specific pattern of cell adhesion receptors whose ex- pression and function is quantitatively and temporally reg- ulated in a very precise manner. Integrins  v  3 and  v  5 are among those receptors that contribute to the coordi- nated cell adhesion and movement of diverse cell types on various ECM components including vitronectin (VN), fi- bronectin (FN), and collagen IV (Coll-IV) (Pelletier et al., Address correspondence to Daniel R. Salomon, Department of Molecular and Experimental Medicine – MEM55, The Scripps Research Insti- tute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. E-mail: dsalomon@scripps.edu 1 Abbreviations used in this paper: Coll-IV, collagen IV; ECM, extracel- lular matrix; FN, fibronectin; LN, laminin; PECAM, platelet endothelial cell adhesion molecule; RGD, arginine, glycine, aspartic acid; VN, vit- ronectin. on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000 on October 11, 2013 jcb.rupress.org Downloaded from Published September 18, 2000