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Department of Pathobiology (Y.Y., X.-M.L., A.M., G.-Q.Z.)
University of Missouri College of Veterinary Medicine Columbia,
Missouri 65211
Hubrecht Laboratory (K.A.L.) Netherlands
Institute for Developmental Biology 3584 CT Utrecht, The
Netherlands
In the mouse embryo, the generation of primordial germ cells (PGCs) from the epiblast requires a bone morphogenetic protein-4 (BMP4) signal from the adjacent extraembryonic ectoderm. In this study, we report that Bmp8b, a member of the Gbb-60A class of the BMP superfamily, is expressed in the extraembryonic ectoderm in pregastrula and gastrula stage mouse embryos and is required for PGC generation. A mutation in Bmp8b on a mixed genetic background results in the absence of PGCs in 43% null mutant embryos and severe reduction 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 homozygous 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 generate double-mutant embryos to study interactions of Bmp8b and Bmp4. Embryos that are double heterozygotes for the Bmp8b and Bmp4 mutations have similar defects in PGC number as Bmp4 heterozygotes, indicating that the effects of the two BMPs are not additive. These findings suggest that BMP4 and BMP8B function as heterodimers and homodimers in PGC specification in the mouse.
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Y. Ying, X. Qi, and G.-Q. Zhao Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways PNAS, July 3, 2001; 98(14): 7858 - 7862. [Abstract] [Full Text] [PDF]
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T. Fujiwara, N. R. Dunn, and B. L. M. Hogan Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse PNAS, November 20, 2001; 98(24): 13739 - 13744. [Abstract] [Full Text] [PDF]
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