Figure 4.

Putative Role of FGF2 in the Mouse Germline Niche

(A) Molecular functions of FGF2 in the germline niche. GDNF expands GFRA1⁺RARG⁻ spermatogonia, whereas FGF2 expands GFRA1⁺RARG⁺ spermatogonia that are a differentiation-prone subset (Ikami et al., 2015). Simultaneously, FGF2 also acts on the germline niche to facilitate RA actions via Cyp26b1 suppression. GDNF suppression might also contribute to expanding GFRA1⁺RARG⁺ spermatogonia.

(B and C) The FGF2-dominant niche is prone to differentiation because of permissiveness for expansion of GFRA1⁺RARG⁺ spermatogonia and RA actions (B), whereas the GDNF-dominant niche is prone to regeneration (C). Indeed, transplanted undifferentiated spermatogonia are prone to proliferation rather than differentiation in germ cell-depleted testes (Nagano et al., 1999, Nagai et al., 2012, Zohni et al., 2012). The present study also demonstrated that busulfan-mediated germ cell depletion increased the Gdnf/Fgf2 ratio in the testis (Figure S1).

See also Figure S1.