An essential role of Bmp4 in the atrioventricular septation of the mouse heart.
Proper septation and valvulogenesis during cardiogenesis depend on interactions between the myocardium and the endocardium. By combining use of a hypomorphic Bone morphogenetic protein 4 (Bmp4) allele with conditional gene inactivation, we here identify Bmp4 as a signal from the myocardium directly mediating atrioventricular septation. Defects in this process cause one of the most common human congenital heart abnormalities, atrioventricular canal defect (AVCD). The spectrum of defects obtained through altering Bmp4 expression in the myocardium recapitulates the range of AVCDs diagnosed in patients, thus providing a useful genetic model with AVCD as the primary defect.
Jiao
Kai
K
Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Kulessa
Holger
H
Tompkins
Kevin
K
Zhou
Yingna
Y
Batts
Lorene
L
Baldwin
H Scott
HS
Hogan
Brigid L M
BL
D000818:Animals; D000831:Animals, Newborn; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000502:physiology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2
C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2