TY - JOUR
T1 - Antibodies to the type II TGFβ receptor block cell activation and migration during atrioventricular cushion transformation in the heart
AU - Brown, Christopher B.
AU - Boyer, Angelique S.
AU - Runyan, Raymond B.
AU - Barnett, Joey V.
N1 - Funding Information:
The authors acknowledge the excellent technical help of Ms. Michelle Cleggett and the thoughtful comments of Thomas Quert-ermous, Jonas Galper, Lee Limbird, Brigid Hogan, Stephen Brandt, and Graham Carpenter. J.V.B. is an American Heart Association± Tennessee Af®liate Research Investigator. R.B.R. is an Established Investigator of the American Heart Association. C.B.B. is supported by NIH General Medical Sciences institutional training grant GM07628. This work was supported by National Heart Lung and Blood Institute Grants 38649 (R.B.R.) and 42266 (R.B.R.). The M-38 antibody was obtained from the Developmental Studies Hybridoma Bank supported by the NICHD.
PY - 1996/3/15
Y1 - 1996/3/15
N2 - Epithelial-mesenchymal transformation is a critical event in the development of many organ systems including the heart. Descriptive studies have implicated a number of factors in mediating this transformation, including transforming growth factor β (TGFβ). We now report that disruption of a TGFβ signal transduction complex by antibodies directed against the Type II TGFβ receptor blocks both the endocardial cell activation and subsequent migration that constitute transformation in the chick atrioventricular (AV) cushion. The Type II receptor was localized to both endothelial and endocardial cells of the chick embryo. Incubation of AV cushion explants from Stage 14, 16, and 18 embryos with antibody resulted in a blockade of AV endocardial cell transformation by greater than 50% as measured by mesenchyme formation. Similarly, the appearance of procollagen Type I, a marker of endocardial cell transformation, was blocked. In addition, within 2 hr after the incubation of activated Stage 18 explants with Type II antibody the rate of migration of transformed cells was decreased by 50%. These data suggest that TGFβ acts directly on AV cushion endocardial cells to stimulate epithelial mesenchymal transformation and that TGFβ mediates at least two distinct components of AV cushion transformation, activation and migration.
AB - Epithelial-mesenchymal transformation is a critical event in the development of many organ systems including the heart. Descriptive studies have implicated a number of factors in mediating this transformation, including transforming growth factor β (TGFβ). We now report that disruption of a TGFβ signal transduction complex by antibodies directed against the Type II TGFβ receptor blocks both the endocardial cell activation and subsequent migration that constitute transformation in the chick atrioventricular (AV) cushion. The Type II receptor was localized to both endothelial and endocardial cells of the chick embryo. Incubation of AV cushion explants from Stage 14, 16, and 18 embryos with antibody resulted in a blockade of AV endocardial cell transformation by greater than 50% as measured by mesenchyme formation. Similarly, the appearance of procollagen Type I, a marker of endocardial cell transformation, was blocked. In addition, within 2 hr after the incubation of activated Stage 18 explants with Type II antibody the rate of migration of transformed cells was decreased by 50%. These data suggest that TGFβ acts directly on AV cushion endocardial cells to stimulate epithelial mesenchymal transformation and that TGFβ mediates at least two distinct components of AV cushion transformation, activation and migration.
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U2 - 10.1006/dbio.1996.0070
DO - 10.1006/dbio.1996.0070
M3 - Article
C2 - 8631497
AN - SCOPUS:0029966491
SN - 0012-1606
VL - 174
SP - 248
EP - 257
JO - Developmental biology
JF - Developmental biology
IS - 2
ER -