ABSTRACT
The critical importance of germ cells in the propagation of a species has long inspired research into the origin of these cells. It was August Weismann who in 1893 for the first time proposed a mechanism by which the germline would distinguish itself from the soma through the inheritance of what he called germ plasm. In Weismann’s theory, the inheritance of germ plasm components by a small subset of cells determines the germline fate of these cells. Indeed, in many lower organisms germ plasm has been demonstrated to exist as a maternally inherited complex of proteins and RNA that controls germ cell fate determination. But while homologues of germ plasm components have been identified, and have been shown to play a role during mammalian germline differentiation, no higher-order germ plasm complexes have been identified in the fertilized mammalian egg. In fact, in mammals germline determination appears to occur later in development and is a more plastic process that is mainly triggered by extracellular signaling events, a process called epigenesis. This was elegantly demonstrated by Lawson and Hage, who injected lineage tracer into single proximal epiblast cells of day 6.5 murine embryos and analyzed the cell fate of these labeled cells after a period of explant culture. These experiments demonstrated that while some labeled cells gave rise to primordial germ cells (PGCs), they never did so exclusively, suggesting that at day 6.5 lineage determination has not yet occurred. This was further corroborated by Tam and Zhou who performed a series of experiments in which they transplanted cells of the distal epiblast, which would normally give
rise to neuroectoderm, to the proximal epiblast where the founder germ cells are located. Relocation of distal epiblast cells to the germ cell microenvironment redirected the differentiation of these cells toward the germline, suggesting that at day 6.5 of murine development, germline fate determination is plastic and depends largely on signaling cues from the microenvironment. However, the nature and role of these signals is largely unknown. Here we take a look at possible candidate signaling pathways and review their possible role in germline fate determination.
