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...

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Bibliographic Details
Published in:Genes & development 1995-09, Vol.9 (17), p.2105-2116
Main Authors: Winnier, G, Blessing, M, Labosky, P A, Hogan, B L
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Bone Morphogenetic Proteins
Cell Line
Chimera
Crosses, Genetic
Embryonic and Fetal Development
Female
Gastrula - physiology
Gene Targeting
Heterozygote
Homozygote
Male
Mesoderm - cytology
Mesoderm - physiology
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Phenotype
Proteins - genetics
Proteins - physiology
Stem Cells
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.9.17.2105