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Pancreatology. 2010;10(1):74-84. doi: 10.1159/000276895. Epub 2010 Mar 26.

Conservation of the TGFbeta/Labial homeobox signaling loop in endoderm-derived cells between Drosophila and mammals.

Author information

  • 1Department of Medicine, Mayo Clinic, Rochester, Minn., USA.

Abstract

BACKGROUND/AIMS:

Midgut formation in Drosophila melanogaster is dependent upon the integrity of a signaling loop in the endoderm which requires the TGFbeta-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, TGFbeta 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 TGFbeta(1) in pancreatic epithelial cell populations and HoxA1 protein co-localizes with TGFbeta(1) 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 TGFbeta-mediated signaling to gene expression in pancreatic epithelial cell populations, thus suggesting a high degree of conservation for a TGFbeta/labial signaling loop in endoderm-derived cells between Drosophila and mammals. and IAP.

PMID:
20339309
[PubMed - indexed for MEDLINE]
PMCID:
PMC2865486
Free PMC Article

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