Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse.

TLDR

Bone morphogenetic protein‑4 (BMP‑4) is a TGF‑β superfamily signaling molecule related to BMP‑2 and Drosophila decapentaplegic. The study aimed to determine BMP‑4’s role in mouse development. BMP‑4 was inactivated by homologous recombination in embryonic stem cells. Homozygous Bmp‑4 mutants die between 6.5 and 9.5 days post‑conception, fail to express mesodermal markers such as T(Brachyury), and display severe mesodermal and extraembryonic defects, demonstrating that BMP‑4 is essential for gastrulation and mesoderm formation, though some mutants are partially rescued by related proteins or maternal BMP‑4.

Abstract

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.