Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesis.
Vertebrate Bmp2 and Bmp4 diverged from a common ancestral gene and encode closely related proteins. Mice homozygous for null mutations in either gene show early embryonic lethality, thereby precluding analysis of shared functions. In the current studies, we present phenotypic analysis of compound mutant mice heterozygous for a null allele of Bmp2 in combination with null or hypomorphic alleles of Bmp4. Whereas mice lacking a single copy of Bmp2 or Bmp4 are viable and have subtle developmental defects, compound mutants show embryonic and postnatal lethality due to defects in multiple organ systems including the allantois, placental vasculature, ventral body wall, skeleton, eye and heart. Within the heart, BMP2 and BMP4 function coordinately to direct normal lengthening of the outflow tract, proper positioning of the outflow vessels, and septation of the atria, ventricle and atrioventricular canal. Our results identify numerous BMP4-dependent developmental processes that are also very sensitive to BMP2 dosage, thus revealing novel functions of Bmp2.
Goldman
Devorah C
DC
Department of Cell and Developmental Biology, Oregon Health and Sciences University, School of Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Donley
Nathan
N
Christian
Jan L
JL
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D001842:Bone and Bones / Q000002:abnormalities; D049033:Chorioallantoic Membrane / Q000196:embryology / Q000378:metabolism; D003433:Crosses, Genetic; D020964:Embryo Loss / Q000235:genetics; D047108:Embryonic Development; D005121:Extremities / Q000196:embryology; D005123:Eye / Q000196:embryology; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000378:metabolism; D017353:Gene Deletion; D005838:Genotype; D006325:Heart Atria / Q000002:abnormalities / Q000196:embryology; D006330:Heart Defects, Congenital; D006352:Heart Ventricles / Q000002:abnormalities / Q000196:embryology; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D038081:Organogenesis
C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4