Slug is an essential target of TGFβ2 signaling in the developing chicken heart

Laura A. Romano, Raymond B Runyan

Research output: Contribution to journalArticle

137 Citations (Scopus)

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-TGFν2 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. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)91-102
Number of pages12
JournalDevelopmental Biology
Volume223
Issue number1
DOIs
StatePublished - Jul 1 2000

Fingerprint

Gastropoda
Epithelial-Mesenchymal Transition
Chickens
Epithelial Cells
Anti-Idiotypic Antibodies
Tretinoin
Endocardial Cushions
Oligodeoxyribonucleotides
Pertussis Toxin
Transfection
Signal Transduction

Keywords

  • BMP
  • Cardiac development
  • Endocardial cushions
  • HGF
  • Noggin
  • Retinoic acid
  • Transcription factor
  • Valve formation
  • Zinc finger protein

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Slug is an essential target of TGFβ2 signaling in the developing chicken heart. / Romano, Laura A.; Runyan, Raymond B.

In: Developmental Biology, Vol. 223, No. 1, 01.07.2000, p. 91-102.

Research output: Contribution to journalArticle

@article{2c4cd30c9847404dace156de1e2d30af,
title = "Slug is an essential target of TGFβ2 signaling in the developing chicken heart",
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-TGFν2 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. (C) 2000 Academic Press.",
keywords = "BMP, Cardiac development, Endocardial cushions, HGF, Noggin, Retinoic acid, Transcription factor, Valve formation, Zinc finger protein",
author = "Romano, {Laura A.} and Runyan, {Raymond B}",
year = "2000",
month = "7",
day = "1",
doi = "10.1006/dbio.2000.9750",
language = "English (US)",
volume = "223",
pages = "91--102",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Slug is an essential target of TGFβ2 signaling in the developing chicken heart

AU - Romano, Laura A.

AU - Runyan, Raymond B

PY - 2000/7/1

Y1 - 2000/7/1

N2 - 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-TGFν2 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. (C) 2000 Academic Press.

AB - 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-TGFν2 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. (C) 2000 Academic Press.

KW - BMP

KW - Cardiac development

KW - Endocardial cushions

KW - HGF

KW - Noggin

KW - Retinoic acid

KW - Transcription factor

KW - Valve formation

KW - Zinc finger protein

UR - http://www.scopus.com/inward/record.url?scp=0034235433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034235433&partnerID=8YFLogxK

U2 - 10.1006/dbio.2000.9750

DO - 10.1006/dbio.2000.9750

M3 - Article

C2 - 10864463

AN - SCOPUS:0034235433

VL - 223

SP - 91

EP - 102

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 1

ER -