Requirement of Bmp8b for the Generation of Primordial Germ Cells in the Mouse

Abstract

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.

Ontogenèse des cellules germinales primordiales

“…Bmp8b interviendrait, comme Bmp4, dans la détermination des PGC, mais pas dans leur prolifération ni dans leur survie. En effet, chez certains embryons homozygotes dépourvus de Bmp8b, lorsque des PGC sont retrouvées, elles migrent et prolifèrent de façon comparable à ce qui est observé chez les embryons hétérozygotes [20,21]. [22].…”

SMAD expression in the testis: An insight into BMP regulation of spermatogenesis

“…The impact of numerous BMPs on the survival and proliferation of murine germ cells during embryonic development and the regulation of postnatal germ cell and somatic cell populations has been identified from in vitro and in vivo studies (Jorgez et al, 2005;Loveland and Hime, 2005;Itman et al, 2006). BMP4, BMP8a, and BMP8b regulate primordial germ cell (PGC) specification in the fetus (Ying et al, 2000;Ying and Zhao, 2001), whereas in in vitro assays, BMP2 and BMP4 enhance juvenile spermatogonial proliferation (Pellegrini et al, 2003;Puglisi et al, 2004) and BMP4 can influence spermatogonial differentiation (Pellegrini et al, 2003;Baleato et al, 2005). BMP8b has also been implicated in the regulation of prepubertal germ cell proliferation at the onset of spermatogenesis, while BMP4, BMP8a and BMP8b are required for complete maintenance of adult spermatogenesis in vivo (Zhao et al, 1996;1998;Hu et al, 2004).…”

Genetics of germ cell development

“…The additional BMP family members BMP8b and BMP2, coming from the extraembryonic ectoderm, oppose the inhibitory anterior signal, setting up a gradient of inhibition and supporting induction of germ cells in the posterior epiblast. 20,[24][25][26] During this time, the pluripotency-associated genes Oct4, Sox2, and Nanog are progressively restricted to the germline and become germ cell specific at E8.0. [27][28][29] The means by which a limited subset of cells is initially selected from among the larger number of competent cells in the correct position of the posterior epiblast is unclear.…”