Faculty Collaboration Database

Conservation of the TGFbeta/Labial homeobox signaling loop in endoderm-derived cells between Drosophila and mammals. Pancreatology 2010;10(1):74-84

Date

03/27/2010

Pubmed ID

20339309

Pubmed Central ID

PMC2865486

DOI

10.1159/000276895

Scopus ID

2-s2.0-77949871512 (requires institutional sign-in at Scopus site)   3 Citations

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.

Author List

Lomberk GA, Imoto I, Gebelein B, Urrutia R, Cook TA

Authors

Gwen Lomberk PhD Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Base Sequence
Drosophila Proteins
Drosophila melanogaster
Endoderm
Gene Expression Regulation, Developmental
Genes, Homeobox
Homeodomain Proteins
Molecular Sequence Data
Pancreas, Exocrine
Rats
Transcription Factors
Transcriptional Activation
Transforming Growth Factor beta