title: Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling.
abstract: 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.
authors.affiliation: Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Selever
authors.forename: Degang
authors.initials: D
authors.lastname: Wang
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Lu
authors.forename: Kelvin A
authors.initials: KA
authors.lastname: Moses
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
mesh_terms: 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
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta