We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Endothelium-Derived Netrin-4 Supports Pancreatic Epithelial Cell Adhesion and Differentiation through Integrins &agr;2&bgr;1 and &agr;3&bgr;1.
- Authors
Yebra, Mayra; Diaferia, Giuseppe R.; Montgomery, Anthony M. P.; Kaido, Thomas; Brunken, William J.; Koch, Manuel; Hardiman, Gary; Crisa, Laura; Cirulli, Vincenzo
- Abstract
Background: Netrins have been extensively studied in the developing central nervous system as pathfinding guidance cues, and more recently in non-neural tissues where they mediate cell adhesion, migration and differentiation. Netrin-4, a distant relative of Netrins 1-3, has been proposed to affect cell fate determination in developing epithelia, though receptors mediating these functions have yet to be identified. Methodology/Principal Findings: Using human embryonic pancreatic cells as a model of developing epithelium, here we report that Netrin-4 is abundantly expressed in vascular endothelial cells and pancreatic ductal cells, and supports epithelial cell adhesion through integrins &agr;2&bgr;1and &agr;3&bgr;1. Interestingly, we find that Netrin-4 recognition by embryonic pancreatic cells through integrins &agr;2&bgr;1and &agr;3&bgr;1 promotes insulin and glucagon gene expression. In addition, full genome microarray analysis revealed that fetal pancreatic cell adhesion to Netrin-4 causes a prominent down-regulation of cyclins and upregulation of negative regulators of the cell cycle. Consistent with these results, a number of other genes whose activities have been linked to developmental decisions and/or cellular differentiation are up-regulated. Conclusions/Significance: Given the recognized function of blood vessels in epithelial tissue morphogenesis, our results provide a mechanism by which endothelial-derived Netrin-4 may function as a pro-differentiation cue for adjacent developing pancreatic cell populations expressing adhesion receptors &agr;2&bgr;1and &agr;3&bgr;1 integrins.
- Subjects
VASCULAR endothelium; NETRINS; CENTRAL nervous system; FETAL tissues; EPITHELIUM; CELL adhesion; CELL differentiation; MORPHOGENESIS
- Publication
PLoS ONE, 2011, Vol 6, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0022750