Gene Expression Profiling of a Mouse Model of Pancreatic Islet Dysmorphogenesis
Open Access
- 20 February 2008
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 3 (2), e1611
- https://doi.org/10.1371/journal.pone.0001611
Abstract
In the past decade, several transcription factors critical for pancreas organogenesis have been identified. Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor Hnf6 specifically in the pancreatic endocrine cell lineage resulted in disruptions in islet morphogenesis, including dysfunctional endocrine cell sorting, increased individual islet size, increased number of peripheral endocrine cell types, and failure of islets to migrate away from the ductal epithelium. The mechanisms whereby maintained Hnf6 causes defects in islet morphogenesis have yet to be elucidated. We exploited the dysmorphic islets in Hnf6 transgenic animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals. Here we report the identification of genes with an altered expression in Hnf6 transgenic animals and highlight factors with potential importance in islet morphogenesis. Importantly, gene products involved in cell adhesion, cell migration, ECM remodeling and proliferation were found to be altered in Hnf6 transgenic pancreata, revealing specific candidates that can now be analyzed directly for their role in these processes during islet development. This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature β cell function.Keywords
This publication has 86 references indexed in Scilit:
- Increased Expression of Hepatocyte Nuclear Factor 6 Stimulates Hepatocyte Proliferation During Mouse Liver RegenerationGastroenterology, 2006
- Gene regulatory factors in pancreatic developmentDevelopmental Dynamics, 2003
- The Rab27a/Granuphilin Complex Regulates the Exocytosis of Insulin-Containing Dense-Core GranulesMolecular and Cellular Biology, 2002
- Diabetes Mellitus and Exocrine Pancreatic Dysfunction in Perk−/− Mice Reveals a Role for Translational Control in Secretory Cell SurvivalMolecular Cell, 2001
- The Reg gene family and Reg proteins: with special attention to the regeneration of pancreatic ?-cellsJournal of Hepato-Biliary-Pancreatic Surgery, 1999
- Insulin-promoter-factor 1 is required for pancreas development in miceNature, 1994
- Homologous but not heterologous contact increases the insulin secretion of individual pancreatic B-cellsExperimental Cell Research, 1989
- Differentiation of prospective mouse pancreatic islet cells during development in vitro and during regenerationDevelopmental Biology, 1987
- Electrophysiological evidence for coupling between β cells of pancreatic isletsNature, 1976
- An ultrastructural analysis of the developing embryonic pancreasDevelopmental Biology, 1972