title: 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.
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 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 undifferentiated progenitors residing within the ductal epithelium of the fetal 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 alpha(v)beta(3) and alpha(v)beta(5), two integrins known to coordinate epithelial cell adhesion 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 alpha(v)beta(3) and alpha(v)beta(5) integrins are developmentally regulated during pancreatic islet ontogeny, and mediate adhesion and migration of putative endocrine 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. Conversely, expression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancreatic ducts. Thus, these data provide the first evidence 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.
authors.affiliation: The Islet Research Laboratory at The Whittier Institute for Diabetes, La Jolla, California, USA.
authors.forename: V
authors.initials: V
authors.lastname: Cirulli
authors.forename: G M
authors.initials: GM
authors.lastname: Beattie
authors.forename: G
authors.initials: G
authors.lastname: Klier
authors.forename: M
authors.initials: M
authors.lastname: Ellisman
authors.forename: C
authors.initials: C
authors.lastname: Ricordi
authors.forename: V
authors.initials: V
authors.lastname: Quaranta
authors.forename: F
authors.initials: F
authors.lastname: Frasier
authors.forename: J K
authors.initials: JK
authors.lastname: Ishii
authors.forename: A
authors.initials: A
authors.lastname: Hayek
authors.forename: D R
authors.initials: DR
authors.lastname: Salomon
mesh_terms: D000328:Adult; D000367:Age Factors; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology / Q000637:transplantation; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000378:metabolism; D016332:Fetal Tissue Transplantation; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D016023:Integrins / Q000032:analysis / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D009842:Oligopeptides / Q000032:analysis / Q000378:metabolism; D016035:Pancreas Transplantation; D010183:Pancreatic Ducts / Q000166:cytology / Q000196:embryology / Q000502:physiology; D019030:Receptors, Vitronectin / Q000032:analysis / Q000235:genetics*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*
chemical_list: D016326:Extracellular Matrix Proteins; D016023:Integrins; D009842:Oligopeptides; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; C047981:arginyl-glycyl-aspartic acid