The TGFβ type II receptor plays a critical role in the endothelial cells during cardiac development.
TGFβ signalling is required for normal cardiac development. To investigate which cell types are involved, we used mice carrying a floxed Type II TGFβ receptor (Tgfbr2fl) allele and Cre-lox genetics to deplete this receptor in different regions of the heart. The three target tissues and corresponding Cre transgenic lines were atrioventricular myocardium (using cGata6-Cre), ventricular myocardium (using Mlc2v-Cre), and vascular endothelium (using tamoxifen-activated Cdh5(PAC)-CreERT2). Spatio-temporal Cre activity in each case was tracked via lacZ activation from the Rosa26R locus. Atrioventricular-myocardial-specific Tgfbr2 knockout (KO) embryos had short septal leaflets of the tricuspid valve, whereas ventricular myocardial-specific KO embryos mainly exhibited a normal cardiac phenotype. Inactivation of Tgfbr2 in endothelial cells from E11.5 resulted in deficient ventricular septation, accompanied by haemorrhage from cerebral blood vessels. We conclude that TGFβ signalling through the Tgfbr2 receptor, in endothelial cells, plays an important role in cardiac development, and is essential for cerebral vascular integrity.
Robson
Andrew
A
Institute of Human Genetics, Newcastle University, Newcastle, United Kingdom.
Allinson
Kathleen R
KR
Anderson
Robert H
RH
Henderson
Deborah J
DJ
Arthur
Helen M
HM
D000818:Animals; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000196:embryology / Q000254:growth & development; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II