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.