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ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum
Author(s) -
Wang Qian,
Elghazi Lynda,
Martin Sophie,
Martins Isabelle,
Srinivasan R. Satish,
Geng Xin,
Sleeman Mark,
Collombat Patrick,
Houghton Janet,
SosaPineda Beatriz
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21379
Subject(s) - pax4 , biology , enteroendocrine cell , pancreas , endocrine system , glucagon , medicine , endocrinology , microbiology and biotechnology , hormone , homeobox , gene , gene expression , genetics
Pax4 ‐deficient mice have a severe gastrointestinal endocrine deficiency: they lack most pancreatic cells that produce insulin or somatostatin and various duodenal endocrine cell types. Remarkably, Pax4 ‐deficient mice also have an overabundance of ghrelin‐expressing cells in the pancreas and duodenum. Detailed analysis of the Pax4 nullizygous pancreas determined that the mutant islets are largely composed of a distinctive endocrine cell type that expresses ghrelin, glucagon, islet amyloid polypeptide (IAPP), and low levels of Pdx1. Lineage‐tracing analysis revealed that most of these unique endocrine cells directly arose from Pax4 ‐deficient progenitors. Previous in vitro work reported that Pax4 is a transcriptional repressor of islet amyloid polypeptide ( IAPP ) and glucagon . In this study, we expanded those results by showing that Pax4 is also a repressor of gherlin . Together, our data further support the notion that Pax4 activity is necessary to establish appropriate patterns of gene expression in endocrine progenitors of the digestive tract. Developmental Dynamics 237:51–61, 2008. © 2007 Wiley‐Liss, Inc.