title: Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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 beta cell function.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Wilding Crawford
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tweedie Ables
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Oh
authors.forename: Braden
authors.initials: B
authors.lastname: Boone
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: Maureen
authors.initials: M
authors.lastname: Gannon
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D023281:Genomics; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics; D007515:Islets of Langerhans / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D010182:Pancreatic Diseases / Q000196:embryology / Q000235:genetics*
chemical_list: D051559:Hepatocyte Nuclear Factor 6; C496606:Onecut1 protein, mouse