TY - JOUR
T1 - Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesis
AU - Goldman, Devorah C.
AU - Donley, Nathan
AU - Christian, Jan L.
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - BMP redundancy
KW - BMP2
KW - BMP4
KW - Bone morphogenetic protein
KW - Embryonic patterning
KW - Heart development
KW - Mouse mutant
UR - http://www.scopus.com/inward/record.url?scp=59849089934&partnerID=8YFLogxK
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U2 - 10.1016/j.mod.2008.11.008
DO - 10.1016/j.mod.2008.11.008
M3 - Article
C2 - 19116164
AN - SCOPUS:59849089934
SN - 0925-4773
VL - 126
SP - 117
EP - 127
JO - Mechanisms of Development
JF - Mechanisms of Development
IS - 3-4
ER -