Conservation of the TGFβ/labial homeobox signaling loop in endoderm-derived cells between drosophila and mammals

Gwen A. Lomberk, Issei Imoto, Brian Gebelein, Raul Urrutia, Tiffany A. Cook

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background/Aims: Midgut formation in Drosophila melanogaster is dependent upon the integrity of a signaling loop in the endoderm which requires the TGFβ-related peptide, Decapentaplegic, and the Hox transcription factor, Labial. Interestingly, although Labial-like homeobox genes are present in mammals, their participation in endoderm morphogenesis is not clearly understood. Methods: We report the cloning, expression, localization, TGFβ inducibility, and biochemical properties of the mammalian Labial-like homeobox, HoxA1, in exocrine pancreatic cells that are embryologically derived from the gut endoderm. Results: HoxA1 is expressed in pancreatic cell populations as two alternatively spliced messages, encoding proteins that share their N-terminal domain, but either lack or include the homeobox at the C-terminus. Transcriptional regulatory assays demonstrate that the shared N-terminal domain behaves as a strong transcriptional activator in exocrine pancreatic cells. HoxA1 is an early response gene for TGFβ1 in pancreatic epithelial cell populations and HoxA1 protein co-localizes with TGFβ1 receptors in the embryonic pancreatic epithelium at a time when exocrine pancreatic morphogenesis occurs (days E16 and E17). Conclusions: These results report a role for HoxA1 in linking TGFβ-mediated signaling to gene expression in pancreatic epithelial cell populations, thus suggesting a high degree of conservation for a TGFβ/labial signaling loop in endoderm-derived cells between Drosophila and mammals.

Original languageEnglish (US)
Pages (from-to)74-84
Number of pages11
JournalPancreatology
Volume10
Issue number1
DOIs
StatePublished - Apr 2010

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Keywords

  • AR4IP
  • Ductular pancreas
  • Early response gene
  • Labial
  • Transactivation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

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