BMPR ENCODES A TYPE-I BONE MORPHOGENETIC PROTEIN-RECEPTOR THAT IS ESSENTIAL FOR GASTRULATION DURING MOUSE EMBRYOGENESIS

Bone morphogenetic proteins (BMPs) are secreted proteins that interact with cell-surface receptors and are believed to play a variety of imp ortant roles during vertebrate embryogenesis. Bmpr, also known as ALK- 3 and Brk-1, encodes a type I transforming growth factor-beta (TGF-bet a) family receptor for BMP-2 and BMP-4. Bmpr is expressed ubiquitously during early mouse embryogenesis and in most adult mouse tissues. To study the function of Bmpr during mammalian development, we generated Bmpr-mutant mice. After embryonic day 9.5 (E9.5), no homozygous mutant s were recovered from heterozygote matings. Homozygous mutants with mo rphological defects were first detected at E7.0 and were smaller than normal. Morphological and molecular examination demonstrated that no m esoderm had formed in the mutant embryos. The growth characteristics o f homozygous mutant blastocysts cultured in vitro were indistinguishab le from those of controls; however, embryonic ectoderm (epiblast) cell proliferation was reduced in all homozygous mutants at E6.5 before mo rphological abnormalities had become prominent. Teratomas arising from E7.0 mutant embryos contained derivatives from all three germ layers but were smaller and gave rise to fewer mesodermal cell types, such as muscle and cartilage, than controls. These results suggest that signa ling through this type I BMP-2/4 receptor is not necessary for preimpl antation or for initial postimplantation development but may be essent ial for the inductive events that lead to the formation of mesoderm du ring gastrulation and later for the differentiation of a subset of mes odermal cell types.