The ability to generate EG cell colonies from PGCs declines beyond 11.5 dpc, with only male EG cells being obtained from 12.5 dpc embryos. Reduced expression of an FGF receptor in female cells provides an explanation for this observation and suggests a mechanism. In both male and female germ cells, c-kit RNA levels decline at 13.5 dpc. It is interesting to speculate that a function of FGFR activation is to maintain c-kit expression in PGCs, thereby contributing to the proliferative stage. This model would predict that in females, FGF receptor expression is reduced by 13.5 dpc, such that the down-regulation of c-kit cannot be prevented by treatment with bFGF. In male PGCs, continuing FGFR expression and subsequent activation may maintain c-kit expression. antibiotics levaquin
When transplanted back into an animal, EG cells can generate teratomas and teratocarcinomas (unpublished results). If a combination of SLF, LIF, and FGF is sufficient to increase the proliferative potential of PGCs resulting in EG cells, what are the limits on PGC proliferation in vivo? Two explanations seem possible. First, in vivo, soluble factors may limit PGC growth. As suggested from the work of Godin and Wylie, members of the transforming growth factor p family may be candidates for such an activity. Bone morphogenetic protein 2, a member of the transforming growth factor p family, is known to reverse the positive effects of FGF-4 on limb bud development, suggesting that an analogous system may limit PGC growth. Alternatively, PGC growth may be limited by physical isolation from one or more factors. In this regard, it is interesting to speculate that FGFs may not be widely expressed in the genital ridge. As PGCs enter the genital ridge they may become isolated from one or more FGFs, contributing to the cessation of proliferation. Further examination of the expression patterns of FGFs and FGFRs in the developing gonad may help elucidate the role of FGFs in germline development.