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Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse
G Winnier1, M Blessing, P A Labosky
1Howard Hughes Medical Institute, Vanderbilt University Medical School, Nashville, Tennessee 37232-2175, USA.
Genes & Development
|September 1, 1995
Summary
Bone morphogenetic protein-4 (BMP-4) is crucial for early mouse development, particularly gastrulation and mesoderm formation. Gene inactivation leads to embryonic lethality, highlighting BMP-4
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Bone morphogenetic protein-4 (BMP-4) is a signaling molecule in the TGF-beta superfamily.
- BMP-4 is closely related to BMP-2 and Drosophila decapentaplegic (DPP).
Purpose of the Study:
- To elucidate the role of BMP-4 in mouse embryonic development.
- To investigate the consequences of BMP-4 gene inactivation.
Main Methods:
- Gene inactivation in mouse embryonic stem (ES) cells using homologous recombination.
- Analysis of homozygous mutant embryos at various developmental stages (6.5-9.5 days post-coitum).
Main Results:
- Homozygous Bmp-4 mutant embryos exhibit lethality between 6.5 and 9.5 days post-coitum.
- Most mutants fail to progress beyond the egg cylinder stage, showing impaired mesoderm formation and lack of T(Brachyury) expression.
- Some mutants develop further but display developmental retardation, truncated posterior structures, and reduced extraembryonic mesoderm.
Conclusions:
- BMP-4 is essential for gastrulation and mesoderm formation in early mouse development.
- Partial rescue in homozygous mutants suggests potential compensation by maternal BMP-4 or related proteins.