Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling.
The Bmp4 signaling molecule is expressed in ventral splanchnic and branchial-arch mesoderm and outflow-tract (OFT) myocardium, suggesting a role for Bmp4 in OFT development. Inactivation of Bmp4 in the caudal branchial arch and splanchnic mesoderm and OFT myocardium by using a conditional null allele of Bmp4 and the Nkx2.5cre recombinase allele resulted in abnormal morphogenesis of branchial-arch arteries (BAAs) and defective OFT septation. Expression of aortic-sac myocardial markers was reduced and expression of the sm22LacZ transgene, a smooth-muscle marker, was attenuated in BAAs and conotruncus of Nkx2.5cre; Bmp4 conditional mutants. Moreover, we found tissue-specific functions for Bmp4 in the regulation of cellular proliferation and apoptosis. We also demonstrate a strong genetic interaction between Bmp4 and Bmp7 in OFT development. Our findings uncover a previously uncharacterized function for Bmp4 in vascular remodeling of the BAAs, and they show definitively that Bmp4, in cooperation with Bmp7, has a central role in OFT septation.
Liu
Wei
W
Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 Holcombe Boulevard, Houston, TX 77030, USA.
Selever
Jennifer
J
Wang
Degang
D
Lu
Mei-Fang
MF
Moses
Kelvin A
KA
Schwartz
Robert J
RJ
Martin
James F
JF
D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology*; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001934:Branchial Region / Q000098:blood supply*; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D009024:Morphogenesis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta