Elsevier

Developmental Biology

Volume 223, Issue 1, 1 July 2000, Pages 91-102
Developmental Biology

Regular Article
Slug is an Essential Target of TGFβ2 Signaling in the Developing Chicken Heart

https://doi.org/10.1006/dbio.2000.9750Get rights and content
Under an Elsevier user license
open archive

Abstract

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-TGFβ2 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 TGFβ2 or other signaling factors regulate Slug expression during EMT in the heart, we cultured AV canal explants in the presence of anti-TGFβ2 antibody, anti-TGFβ3 antibody, pertussis toxin, retinoic acid, noggin, or anti-HGF antibody. Only treatment with anti-TGFβ2 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-TGFβ2 antibody but not retinoic acid on EMT. Slug is thus an essential target of TGFβ2 signaling during EMT in the developing chicken heart.

Keywords

BMP
cardiac development
endocardial cushions
HGF
noggin
retinoic acid
transcription factor
valve formation
zinc finger protein

Cited by (0)

1

Present address: Department of Zoology, Duke University, Durham, NC 27708.

2

To whom correspondence should be addressed.