TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart

Angelique S. Boyer, Ingrid I. Ayerinskas, Eric B. Vincent, Lisa A. McKinney, Daniel L. Weeks, Raymond B Runyan

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Heart valve formation is initiated by an epithelial-mesenchymal cell transformation (EMT) of endothelial cells in the atrioventricular (AV) canal. Mesenchymal cells formed from cardiac EMTs are the initial cellular components of the cardiac cushions and progenitors of valvular and septal fibroblasts. It has been shown that transforming growth factor β (TGFβ) mediates EMT in the AV canal, and TGFβ1 and 2 isoforms are expressed in the mouse heart while TGFβ2 and 3 are expressed in the avian heart. Depletion of TGFβ3 in avian or TGFβ2 in mouse leads to developmental defects of heart tissue. These observations raise questions as to whether multiple TGFβ isoforms participate in valve formation. In this study, we examined the localization and function of TGFβ2 and TGFβ3 in the chick heart during EMT. TGFβ2 was present in both endothelium and myocardium before and after EMT. TGFβ2 antibody inhibited endothelial cell-cell separation. In contrast, TGFβ3 was present only in the myocardium before EMT and was in the endothelium at the initiation of EMT. TGFβ3 antibodies inhibited mesenchymal cell formation and migration into the underlying matrix. Both TGFβ2 and 3 increased fibrillin 2 expression. However, only TGFβ2 treatment increased cell surface β-1,4-galactosyltransferase expression. These data suggest that TGFβ2 and TGFβ3 are sequentially and separately involved in the process of EMT. TGFβ2 mediates initial endothelial cell-cell separation while TGFβ3 is required for the cell morphological change that enables the migration of cells into the underlying ECM.

Original languageEnglish (US)
Pages (from-to)530-545
Number of pages16
JournalDevelopmental Biology
Volume208
Issue number2
DOIs
StatePublished - Apr 15 1999

Fingerprint

Epithelial-Mesenchymal Transition
Epithelial Cells
Endothelial Cells
Cell Separation
Transforming Growth Factors
Endothelium
Cell Movement
Myocardium
Protein Isoforms
Galactosyltransferases
Antibodies
Heart Valves
Fibroblasts

Keywords

  • Cardiogenesis
  • Cushion formation
  • Valve development

ASJC Scopus subject areas

  • Developmental Biology

Cite this

TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. / Boyer, Angelique S.; Ayerinskas, Ingrid I.; Vincent, Eric B.; McKinney, Lisa A.; Weeks, Daniel L.; Runyan, Raymond B.

In: Developmental Biology, Vol. 208, No. 2, 15.04.1999, p. 530-545.

Research output: Contribution to journalArticle

Boyer, Angelique S. ; Ayerinskas, Ingrid I. ; Vincent, Eric B. ; McKinney, Lisa A. ; Weeks, Daniel L. ; Runyan, Raymond B. / TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. In: Developmental Biology. 1999 ; Vol. 208, No. 2. pp. 530-545.
@article{ada4cc118326464f98ba88ece5f5ec56,
title = "TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart",
abstract = "Heart valve formation is initiated by an epithelial-mesenchymal cell transformation (EMT) of endothelial cells in the atrioventricular (AV) canal. Mesenchymal cells formed from cardiac EMTs are the initial cellular components of the cardiac cushions and progenitors of valvular and septal fibroblasts. It has been shown that transforming growth factor β (TGFβ) mediates EMT in the AV canal, and TGFβ1 and 2 isoforms are expressed in the mouse heart while TGFβ2 and 3 are expressed in the avian heart. Depletion of TGFβ3 in avian or TGFβ2 in mouse leads to developmental defects of heart tissue. These observations raise questions as to whether multiple TGFβ isoforms participate in valve formation. In this study, we examined the localization and function of TGFβ2 and TGFβ3 in the chick heart during EMT. TGFβ2 was present in both endothelium and myocardium before and after EMT. TGFβ2 antibody inhibited endothelial cell-cell separation. In contrast, TGFβ3 was present only in the myocardium before EMT and was in the endothelium at the initiation of EMT. TGFβ3 antibodies inhibited mesenchymal cell formation and migration into the underlying matrix. Both TGFβ2 and 3 increased fibrillin 2 expression. However, only TGFβ2 treatment increased cell surface β-1,4-galactosyltransferase expression. These data suggest that TGFβ2 and TGFβ3 are sequentially and separately involved in the process of EMT. TGFβ2 mediates initial endothelial cell-cell separation while TGFβ3 is required for the cell morphological change that enables the migration of cells into the underlying ECM.",
keywords = "Cardiogenesis, Cushion formation, Valve development",
author = "Boyer, {Angelique S.} and Ayerinskas, {Ingrid I.} and Vincent, {Eric B.} and McKinney, {Lisa A.} and Weeks, {Daniel L.} and Runyan, {Raymond B}",
year = "1999",
month = "4",
day = "15",
doi = "10.1006/dbio.1999.9211",
language = "English (US)",
volume = "208",
pages = "530--545",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart

AU - Boyer, Angelique S.

AU - Ayerinskas, Ingrid I.

AU - Vincent, Eric B.

AU - McKinney, Lisa A.

AU - Weeks, Daniel L.

AU - Runyan, Raymond B

PY - 1999/4/15

Y1 - 1999/4/15

N2 - Heart valve formation is initiated by an epithelial-mesenchymal cell transformation (EMT) of endothelial cells in the atrioventricular (AV) canal. Mesenchymal cells formed from cardiac EMTs are the initial cellular components of the cardiac cushions and progenitors of valvular and septal fibroblasts. It has been shown that transforming growth factor β (TGFβ) mediates EMT in the AV canal, and TGFβ1 and 2 isoforms are expressed in the mouse heart while TGFβ2 and 3 are expressed in the avian heart. Depletion of TGFβ3 in avian or TGFβ2 in mouse leads to developmental defects of heart tissue. These observations raise questions as to whether multiple TGFβ isoforms participate in valve formation. In this study, we examined the localization and function of TGFβ2 and TGFβ3 in the chick heart during EMT. TGFβ2 was present in both endothelium and myocardium before and after EMT. TGFβ2 antibody inhibited endothelial cell-cell separation. In contrast, TGFβ3 was present only in the myocardium before EMT and was in the endothelium at the initiation of EMT. TGFβ3 antibodies inhibited mesenchymal cell formation and migration into the underlying matrix. Both TGFβ2 and 3 increased fibrillin 2 expression. However, only TGFβ2 treatment increased cell surface β-1,4-galactosyltransferase expression. These data suggest that TGFβ2 and TGFβ3 are sequentially and separately involved in the process of EMT. TGFβ2 mediates initial endothelial cell-cell separation while TGFβ3 is required for the cell morphological change that enables the migration of cells into the underlying ECM.

AB - Heart valve formation is initiated by an epithelial-mesenchymal cell transformation (EMT) of endothelial cells in the atrioventricular (AV) canal. Mesenchymal cells formed from cardiac EMTs are the initial cellular components of the cardiac cushions and progenitors of valvular and septal fibroblasts. It has been shown that transforming growth factor β (TGFβ) mediates EMT in the AV canal, and TGFβ1 and 2 isoforms are expressed in the mouse heart while TGFβ2 and 3 are expressed in the avian heart. Depletion of TGFβ3 in avian or TGFβ2 in mouse leads to developmental defects of heart tissue. These observations raise questions as to whether multiple TGFβ isoforms participate in valve formation. In this study, we examined the localization and function of TGFβ2 and TGFβ3 in the chick heart during EMT. TGFβ2 was present in both endothelium and myocardium before and after EMT. TGFβ2 antibody inhibited endothelial cell-cell separation. In contrast, TGFβ3 was present only in the myocardium before EMT and was in the endothelium at the initiation of EMT. TGFβ3 antibodies inhibited mesenchymal cell formation and migration into the underlying matrix. Both TGFβ2 and 3 increased fibrillin 2 expression. However, only TGFβ2 treatment increased cell surface β-1,4-galactosyltransferase expression. These data suggest that TGFβ2 and TGFβ3 are sequentially and separately involved in the process of EMT. TGFβ2 mediates initial endothelial cell-cell separation while TGFβ3 is required for the cell morphological change that enables the migration of cells into the underlying ECM.

KW - Cardiogenesis

KW - Cushion formation

KW - Valve development

UR - http://www.scopus.com/inward/record.url?scp=0033560169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033560169&partnerID=8YFLogxK

U2 - 10.1006/dbio.1999.9211

DO - 10.1006/dbio.1999.9211

M3 - Article

C2 - 10191064

AN - SCOPUS:0033560169

VL - 208

SP - 530

EP - 545

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -