Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse.
Bone morphogenetic protein-4 (BMP-4) is a member of the TGF-beta superfamily of polypeptide signaling molecules, closely related to BMP-2 and to Drosophila decapentaplegic (DPP). To elucidate the role of BMP-4 in mouse development the gene has been inactivated by homologous recombination in ES cells. Homozygous mutant Bmp-4tm1blh embryos die between 6.5 and 9.5 days p.c., with a variable phenotype. Most Bmp-4tm1blh embryos do not proceed beyond the egg cylinder stage, do not express the mesodermal marker T(Brachyury), and show little or no mesodermal differentiation. Some homozygous mutants develop to the head fold or beating heart/early somite stage or beyond. However, they are developmentally retarded and have truncated or disorganized posterior structures and a reduction in extraembryonic mesoderm, including blood islands. These results provide direct genetic evidence that BMP-4 is essential for several different processes in early mouse development, beginning with gastrulation and mesoderm formation. Moreover, in the presumed absence of zygotic ligand, it appears that homozygous mutants can be rescued partially by related proteins or by maternal BMP-4.
Winnier
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Howard Hughes Medical Institute, Vanderbilt University Medical School, Nashville, Tennessee 37232-2175, USA.
Blessing
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Labosky
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Hogan
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D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins; D002460:Cell Line; D002678:Chimera; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development; D005260:Female; D005775:Gastrula / Q000502:physiology*; D018390:Gene Targeting; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells
D019485:Bone Morphogenetic Proteins; D011506:Proteins