As. Boyer et al., TGF beta 2 and TGF beta 3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart, DEVELOP BIO, 208(2), 1999, pp. 530-545
Heart valve formation is initiated by an epithelial-mesenchymal cell transf
ormation (EMT) of endothelial cells in the atrioventricular (AV) canal. Mes
enchymal 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 beta (TGF beta) mediate
s EMT in the AV canal, and TGF beta 1 and 2 isoforms are expressed in the m
ouse heart while TGF beta 2 and 3 are expressed in the avian heart. Depleti
on of TGF beta 3 in avian or TGF beta 2 in mouse leads to developmental def
ects of heart tissue. These observations raise questions as to whether mult
iple TGF beta isoforms participate in valve formation. In this study, we ex
amined the localization and function of TGF beta 2 and TGF beta 3 in the ch
ick heart during EMT. TGF beta 2 was present in both endothelium and myocar
dium before and after EMT. TGF beta 2 antibody inhibited endothelial cell-c
ell separation. In contrast, TGF beta 3 was present only in the myocardium
before EMT and was in the endothelium at the initiation of EMT. TGF beta 3
antibodies inhibited mesenchymal cell formation and migration into the unde
rlying matrix. Both TGF beta 2 and 3 increased fibrillin 2 expression. Howe
ver, only TGF beta 2 treatment increased cell surface beta-1,4-galactosyltr
ansferase expression. These data suggest that TGF beta 2 and TGF beta 3 are
sequentially and separately involved in the process of EMT. TGF beta 2 med
iates initial endothelial cell-cell separation while TGF beta 3 is required
for the cell morphological change that enables the migration of cells into
the underlying ECM. (C) 1999 Academic Press.