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 allel...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-03, Vol.101 (13), p.4489-4494
Main Authors: Liu, Wei, Selever, Jennifer, Wang, Degang, Lu, Mei-Fang, Moses, Kelvin A., Schwartz, Robert J., Martin, James F., Olson, Eric N.
Format: Article
Language:English
Subjects:
Alleles
Animals
Aorta
Aorta, Thoracic - embryology
Apoptosis
Biological Sciences
Biology
Blood vessels
Bone Morphogenetic Protein 4
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins - deficiency
Bone Morphogenetic Proteins - genetics
Bone Morphogenetic Proteins - physiology
Branchial Region - blood supply
Cell growth
Embryonic and Fetal Development
Embryos
Enzymes
Gene expression
Gene Expression Regulation, Developmental
Genes
Heart - embryology
Mesoderm
Mesoderm - physiology
Mice
Molecules
Morphogenesis
Mutation
Myocardium
Neurons
Renovations
Signal Transduction
Smooth muscle
Transforming Growth Factor beta - physiology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0308466101