Requirement of Bmp8b for the generation of primordial germ cells in the mouse

In the mouse embryo, the generation of primordial germ cells (PGCs) from th e epiblast requires a bone morphogenetic protein-4 (BMP4) signal from the a djacent extraembryonic ectoderm. In this study, we report that Bmp8b, a mem ber of the Gbb-60A class of the BMP superfamily, is expressed in the extrae mbryonic ectoderm in pregastrula and gastrula stage mouse embryos and is re quired for PGC generation, A mutation in Bmp8b on a mixed genetic backgroun d results in the absence of PGCs in 43% null mutant embryos and severe redu ction in PGC number in the remainder. The heterozygotes are unaffected. On a largely C57BL/6 background, Bmp8b null mutants completely lack PGCs, and Bmp8b heterozygotes have a reduced number of PGCs. In addition, Bmp8b homoz ygous null embryos on both genetic backgrounds have a short allantois, and this organ is missing in some more severe mutants. Since Bmp4 heterozygote embryos have reduced numbers of PGCs, we used a genetic approach to generat e double-mutant embryos to study interactions of Bmp8b and Bmp4. Embryos th at are double heterozygotes for the Bmp8b and Bmp4 mutations have similar d efects in PGC number as Bmp4 heterozygotes, indicating that the effects of the two BMPs are not additive. These findings suggest that BMP4 and BMP8B f unction as heterodimers and homodimers in PGC specification in the mouse.