ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum

Qian Wang, Lynda Elghazi, Sophie Martin, Isabelle Martins, R. Satish Srinivasan, Xin Geng, Mark Sleeman, Patrick Collombat, Janet Houghton, Beatriz Sosa-Pineda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)51-61
Number of pages11
JournalDevelopmental Dynamics
Volume237
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Arx
  • Duodenum
  • Endocrine
  • Ghrelin
  • Glucagon
  • HCT8 cells
  • Mouse
  • Pancreas
  • Pax4
  • βTC3 cells

ASJC Scopus subject areas

  • Developmental Biology

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