Signaling of bone morphogenetic protein (BMP) via type I and type II receptors is
involved in multiple processes contributing to cardiogenesis. To investigate the role
of the BMP type II receptor (BMPRII) in heart development, the BMPRII gene was deleted
throughout the embryo during gastrulation using a Mox2-Cre transgene. BMPRII(flox/-);Mox2-Cre
mice exhibited cardiac defects including double-outlet right ventricle, ventricular
septal defect (VSD), atrioventricular (AV) cushion defects, and thickened valve leaflets.
To characterize the tissue-specific functions of BMPRII in cardiogenesis, a series
of Cre transgenes (alphaMHC-, Tie2-, Wnt1-, and SM22alpha-Cre) was employed. Interestingly,
myocardial development was normal when the BMPRII gene was deleted in myocardial cells
using Mox2-Cre, alphaMHC-Cre, or SM22alpha-Cre transgenes, suggesting that signaling
by other BMP type II receptors may compensate for the absence of BMPRII in the myocardial
cells. AV cushion defects including atrial septal defect, membranous VSD, and thickened
valve leaflets were found in BMPRII(flox/-);Tie2-Cre mice. Abnormal positioning of
the aorta was observed in BMPRII(flox/-);Wnt1-Cre and BMPRII(flox/-);SM22alpha-Cre
mice. Taken together, these results demonstrate that endocardial BMPRII expression
is required for septal formation and valvulogenesis. Moreover, mesenchymal BMPRII
expression in the outflow tract cushion is required for proper positioning of the
aorta.