Inactivation of Bmp4 from the Tbx1 expression domain causes abnormal pharyngeal arch artery and cardiac outflow tract remodeling.
Maldevelopment of outflow tract and aortic arch arteries is among the most common forms of human congenital heart diseases. Both Bmp4 and Tbx1 are known to play critical roles during cardiovascular development. Expression of these two genes partially overlaps in pharyngeal arch areas in mouse embryos. In this study, we applied a conditional gene inactivation approach to test the hypothesis that Bmp4 expressed from the Tbx1 expression domain plays a critical role for normal development of outflow tract and pharyngeal arch arteries. We showed that inactivation of Bmp4 from Tbx1-expressing cells leads to the spectrum of deformities resembling the cardiovascular defects observed in human DiGeorge syndrome patients. Inactivation of Bmp4 from the Tbx1 expression domain did not cause patterning defects, but affected remodeling of outflow tract and pharyngeal arch arteries. Our further examination revealed that Bmp4 is required for normal recruitment/differentiation of smooth muscle cells surrounding the PAA4 and survival of outflow tract cushion mesenchymal cells.
Division of Research, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Xuguang
X
Nie
Christopher B
CB
Brown
Qin
Q
Wang
Kai
K
Jiao
D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D017209:Apoptosis; D001158:Arteries / Q000002:abnormalities* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D001934:Branchial Region / Q000002:abnormalities* / Q000098:blood supply* / Q000473:pathology; D018376:Cardiovascular Abnormalities / Q000196:embryology / Q000473:pathology; D002319:Cardiovascular System / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004062:DiGeorge Syndrome / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000473:pathology; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006801:Humans; D019426:Integrases; D051379:Mice; D019683:Penetrance; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000235:genetics*
D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; C045073:Cre recombinase; D019426:Integrases