Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development

Jean Sébastien Annicotte, Elisabeth Fayard, Galvin H. Swift, Lars Selander, Helena Edlund, Toshiya Tanaka, Tatsuhiko Kodama, Kristina Schoonjans, Johan Auwerx

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Liver receptor homolog 1 (LRH-1) and pancreatic-duodenal homeobox 1 (PDX-1) are coexpressed in the pancreas during mouse embryonic development. Analysis of the regulatory region of the human LRH-1 gene demonstrated the presence of three functional binding sites for PDX-1. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis showed that PDX-1 bound to the LRH-1 promoter, both in cultured cells in vitro and during pancreatic development in vivo. Retroviral expression of PDX-1 in pancreatic cells induced the transcription of LRH-1, whereas reduced PDX-1 levels by RNA interference attenuated its expression. Consistent with direct regulation of LRH-1 expression by PDX-1, PDX-1-/- mice expressed smaller amounts of LRH-1 mRNA in the embryonic pancreas. Taken together, our data indicate that PDX-1 controls LRH-1 expression and identify LRH-1 as a novel downstream target in the PDX-1 regulatory cascade governing pancreatic development, differentiation, and function.

Original languageEnglish (US)
Pages (from-to)6713-6724
Number of pages12
JournalMolecular and cellular biology
Volume23
Issue number19
DOIs
StatePublished - Oct 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Annicotte, J. S., Fayard, E., Swift, G. H., Selander, L., Edlund, H., Tanaka, T., Kodama, T., Schoonjans, K., & Auwerx, J. (2003). Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development. Molecular and cellular biology, 23(19), 6713-6724. https://doi.org/10.1128/MCB.23.19.6713-6724.2003