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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Biomarkers, Blotting, Western, Cell Adhesion, Cell Differentiation, Cell Movement, Cell Proliferation, Endothelium, Vascular, Epithelial Cells, Fetus, Fluorescent Antibody Technique, Gene Expression Profiling, Gene Expression Regulation, Developmental, Glucagon, Humans, Immunoenzyme Techniques, Immunoprecipitation, Insulin, Integrin alpha2beta1, Integrin alpha3beta1, Nerve Growth Factors, Netrins, Oligonucleotide Array Sequence Analysis, Pancreatic Ducts, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction.
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Does endothelium-derived Netrin-4 support pancreatic epithelial cell adhesion and differentiation through integrins α2β1 and α3β1? Context: 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. 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 α2β1 and α3β1. Interestingly, we find that Netrin-4 recognition by embryonic pancreatic cells through integrins α2β1 and α3β1 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 up-regulation 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.
assistant
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 α2β1 and α3β1 integrins. Final Decision: yes