Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development.
The ligand specificity of transforming growth factor beta (TGFbeta) in vivo in mouse cardiac cushion epithelial-to-mesenchymal transition (EMT) is poorly understood. To elucidate the function of TGFbeta in cushion EMT, we analyzed Tgfb1(-/-), Tgfb2(-/-), and Tgfb3(-/-) mice between embryonic day (E) 9.5 and E14.5 using both in vitro and in vivo approaches. Atrioventricular (AV) canal collagen gel assays at E9.5 indicated normal EMT in both Tgfb1(-/-) and Tgfb3(-/-) mice. However, analysis of Tgfb2(-/-) AV explants at E9.5 and E10.5 indicated that EMT, but not cushion cell proliferation, was initially delayed but later remained persistent. This was concordant with the observation that Tgfb2(-/-) embryos, and not Tgfb1(-/-) or Tgfb3(-/-) embryos, develop enlarged cushions at E14.5 with elevated levels of well-validated indicators of EMT. Collectively, these data indicate that TGFbeta2, and not TGFbeta1 or TGFbeta3, mediates cardiac cushion EMT by promoting both the initiation and cessation of EMT.
Azhar
Mohamad
M
BIO5 Institute, University of Arizona, Tucson, Arizona, USA. azharm@email.arizona.edu
Runyan
Raymond B
RB
Gard
Connie
C
Sanford
L Philip
LP
Miller
Marian L
ML
Andringa
Anastasia
A
Pawlowski
Sharon
S
Rajan
Sudarsan
S
Doetschman
Thomas
T
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006321:Heart / Q000196:embryology* / Q000502:physiology; D008024:Ligands; D008648:Mesoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000502:physiology; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000502:physiology; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000502:physiology
D008024:Ligands; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3