Misexpression of noggin leads to septal defects in the outflow tract of the chick heart.
BMP-2 and BMP-4 are known to be involved in the early events which specify the cardiac lineage. Their later patterns of expression in the developing mouse and chick heart, in the myocardium overlying the atrioventricular canal (AV) and outflow tract (OFT) cushions, also suggest that they may play a role in valvoseptal development. In this study, we have used a recombinant retrovirus expressing noggin to inhibit the function of BMP-2/4 in the developing chick heart. This procedure resulted in abnormal development of the OFT and the ventricular septum. A spectrum of abnormalities was seen ranging from common arterial trunk to double outlet right ventricle. In hearts infected with noggin virus, where the neural crest cells have been labelled, the results show that BMP-2/4 function is required for the migration of neural crest cells into the developing OFT to form the aortopulmonary septum. Prior to septation, misexpression of noggin also leads to a decrease in the number of proliferating mesenchymal cells within the proximal cushions of the outflow tract. These results suggest that BMP-2/4 function may mediate several key events during cardiac development.
Allen
S P
SP
Department of Craniofacial Development, Guy's, King's and St. Thomas' School of Dentistry, Guy's Tower, Floor 28, London Bridge, London, SE1 9RT, United Kingdom. sallen@rvc.ac.uk
Bogardi
J P
JP
Barlow
A J
AJ
Mir
S A
SA
Qayyum
S R
SR
Verbeek
F J
FJ
Anderson
R H
RH
Francis-West
P H
PH
Brown
N A
NA
Richardson
M K
MK
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins; D002455:Cell Division / Q000502:physiology; D002642:Chick Embryo; D006321:Heart / Q000196:embryology*; D006343:Heart Septal Defects / Q000209:etiology*; D017403:In Situ Hybridization; D009206:Myocardium / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D011506:Proteins; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse