Journal
DEVELOPMENTAL BIOLOGY
Volume 223, Issue 1, Pages 91-102Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/dbio.2000.9750
Keywords
BMP; cardiac development; endocardial cushions; HGF; noggin; retinoic acid; transcription factor; valve formation; zinc finger protein
Categories
Funding
- NHLBI NIH HHS [HL58696] Funding Source: Medline
Ask authors/readers for more resources
An epithelial-mesenchymal cell transformation (EMT) occurs during the development of endocardial cushions in the atrioventricular (AV) canal of the heart. This is a complex developmental process regulated by multiple extracellular signals and signal transduction pathways. It was recently shown that the transcription factor Slug is expressed in the AV canal and is required for initial steps of EMT. Treatment of AV canal explants with either antisense oligodeoxynucleotides toward Slug or anti-TGF beta 2 antibody inhibited initial steps of EMT. Others have identified roles for HGF and BMP during EMT in the heart. Both HGF and BMP are known to regulate Slug in other cell types. To determine whether TGF beta 2 or other signaling factors regulate Slug expression during EMT in the heart, we cultured AV canal explants in the presence of anti-TGF beta 2 antibody, anti-TGF beta 3 antibody, pertussis toxin, retinoic acid, noggin, or anti-HGF antibody. Only treatment with anti-TGF beta 2 antibody or retinoic acid inhibited Slug expression in AV canal explants. Consistent with these data, we found that retinoic acid disrupted initial steps of EMT, while antagonists of BMP and HGF signaling disrupted later steps of EMT. Transfection of AV canal explants with Slug rescued the inhibitory effect of anti-TGF beta 2 antibody but not retinoic acid on EMT. Slug is thus an essential target of TGF beta 2 signaling during EMT in the developing chicken heart. (C) 2000 Academic Press.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available