The role of fGSCs is well-established in several animals reviewed in (Dunlop et al., 2014), in particular “lower” invertebrates such as C. elegans and Drosophila (Fig. 2). In C. elegans, a GSC population is formed in the larvae and, in the adult, these cells maintain a stable population of germ cells and are constantly producing gametes (Kimble, 2011). Around 35-70 GSCs reside in a germ cell niche at the distal end of the gonad, called the distal tip cell (DTC), which maintains their self-renewal properties (Kimble and White, 1981); however, as the GSCs extend outside the niche, they begin to mature and enter meiosis, with maturation occurring in the distal-to-proximal direction (Kimble, 2011). The Notch signaling pathway is a key regulator in this process: it both stimulates GSC mitosis and is essential in repressing meiotic entry, thereby maintaining the GSC population (Kimble, 2011).

Figure 2

In Drosophila, ovaries are made up to 16 to 18 tubes, called ovarioles, and a germ cell niche, containing approximately two GSCs, is found at the tip of each ovariole, termed the germarium (Xie and Spradling, 2000). The niche comprises three different somatic cell types: terminal filament cells at the anterior end of the ovariole, caps cells which are associated with the GSCs and escort cells which prevent the GSCs from touching each other (Spradling et al., 2011). GSCs mitose asymmetrically, forming a GSC and a cystoblast cell, with the former maintaining the GSC population by remaining beside the cap cells, and the latter continuing to divide until 16 germline cysts have been produced. Only one of these cells will become an oocyte, while the remainder become supportive or ‘nurse’ cells (Spradling et al., 2011). The regulatory pathways involved in maintaining the Drosophila GSC population and promoting differentiation are complex but, in brief, the terminal filament cells activate the JAK-STAT signaling pathway within the cap cells which, in turn, induces the production of BMP ligands. In response, the GSCs repress the expression of an inducer of differentiation, bag-of-marbles (bam) and maintain high levels of the translational repressor NANOS, thereby sustaining GSC function and preventing differentiation. Once the GSCs have left the niche, however, they are no longer are exposed to BMP ligands, therefore bam is upregulated and daughter cells can differentiate into germ cells (Spradling et al., 2011).

Female GSCs have also been described in non-mammalian vertebrates, including some species of fish. Teleost fish such as zebrafish (Danio rerio) (Draper et al., 2007) and the medaka (Oryzias latipes) (Nakamura et al., 2010) have been reported to undergo post-natal neo-oogenesis. It has been postulated that the germ cell niche in zebrafish is situated in the germinal zone, a discrete area on the ovarian surface (Beer and Draper, 2013). Furthermore, as in Drosophila, the Nanos protein appears to be essential for ongoing oogenesis in the adult ovary of the zebrafish, with the nanos1, nanos2 and nanos3 genes all implicated in maintaining the fGSC population (Draper et al., 2007, Beer and Draper, 2013). In the medaka, the germ cell niche is termed the germinal cradle and is located in the ovarian cords (Nakamura et al., 2010). Once again, Nanos has been found to be important, with mitotically-active medaka fGSCs expressing nanos2 (Nakamura et al., 2010). The existence of specialised niches across phyla with some similarities in regulatory pathways is indicative of evolutionary conservation within the animal kingdom.