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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.

Cirulli V, Beattie GM, Klier G, Ellisman M, Ricordi C, Quaranta V, Frasier F, Ishii JK, Hayek A, Salomon DR - J. Cell Biol. (2000)

Bottom Line: This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans.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.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.

View Article: PubMed Central - PubMed

Affiliation: The Islet Research Laboratory at The Whittier Institute for Diabetes, La Jolla, California, USA.

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.

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Identification of Coll-IV in the developing human pancreas. Three-color confocal immune fluorescence on cryostat sections of human fetal pancreas. A strong Coll-IV-specific immune reactivity (A, green) identifies basal membranes (A, arrowheads) of cells in the ducts (asterisk), and in clusters of developing islet cells, identified by staining for insulin (C, red) and glucagon (B, blue). The three fluorophore spectra are combined in D. Bar, 100 μm.
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Figure 6: Identification of Coll-IV in the developing human pancreas. Three-color confocal immune fluorescence on cryostat sections of human fetal pancreas. A strong Coll-IV-specific immune reactivity (A, green) identifies basal membranes (A, arrowheads) of cells in the ducts (asterisk), and in clusters of developing islet cells, identified by staining for insulin (C, red) and glucagon (B, blue). The three fluorophore spectra are combined in D. Bar, 100 μm.

Mentions: Immune staining for Coll-IV (Fig. 6) reveals a distinct pattern marking the basal membranes of the epithelial compartment, which includes both ducts and developing islets. Note the strong fluorescent signal defining the basal membranes of the ducts (Fig. 6 A; arrowheads). A similar strong staining highlights the basal membranes of developing pancreatic islets (A; arrow). This pattern suggests that Coll-IV may be required as a pathfinder matrix for endocrine progenitor cells and as a structural template for newly developing islets.


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.

Cirulli V, Beattie GM, Klier G, Ellisman M, Ricordi C, Quaranta V, Frasier F, Ishii JK, Hayek A, Salomon DR - J. Cell Biol. (2000)

Identification of Coll-IV in the developing human pancreas. Three-color confocal immune fluorescence on cryostat sections of human fetal pancreas. A strong Coll-IV-specific immune reactivity (A, green) identifies basal membranes (A, arrowheads) of cells in the ducts (asterisk), and in clusters of developing islet cells, identified by staining for insulin (C, red) and glucagon (B, blue). The three fluorophore spectra are combined in D. Bar, 100 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2150716&req=5

Figure 6: Identification of Coll-IV in the developing human pancreas. Three-color confocal immune fluorescence on cryostat sections of human fetal pancreas. A strong Coll-IV-specific immune reactivity (A, green) identifies basal membranes (A, arrowheads) of cells in the ducts (asterisk), and in clusters of developing islet cells, identified by staining for insulin (C, red) and glucagon (B, blue). The three fluorophore spectra are combined in D. Bar, 100 μm.
Mentions: Immune staining for Coll-IV (Fig. 6) reveals a distinct pattern marking the basal membranes of the epithelial compartment, which includes both ducts and developing islets. Note the strong fluorescent signal defining the basal membranes of the ducts (Fig. 6 A; arrowheads). A similar strong staining highlights the basal membranes of developing pancreatic islets (A; arrow). This pattern suggests that Coll-IV may be required as a pathfinder matrix for endocrine progenitor cells and as a structural template for newly developing islets.

Bottom Line: This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans.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.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.

View Article: PubMed Central - PubMed

Affiliation: The Islet Research Laboratory at The Whittier Institute for Diabetes, La Jolla, California, USA.

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.

Show MeSH
Related in: MedlinePlus