Fig. 6

Proposed model for FGF and MEK1/2 signalling in testis and male germline development. In the developing testis, SOX9 and FGF9 promote Sertoli cell proliferation and organisation. It has been proposed that FGF9 drives both germ stem cell characteristics and male germline differentiation. Sertoli cells indirectly promote male germline differentiation, including mitotic arrest and expression of male germline markers such as Nanos2, Dppa4 and Dnmt3L. MEK1/2 signalling inhibition results in failed germ cell mitotic arrest, failed upregulation of male germline markers including Nanos2, DPPA4 and DNMT3L and maintained expression of the pluripotency marker, Nanog. Although FGF signalling promotes Sertoli cell development and stem cell characteristics in foetal germ cells, it is dispensable for male germline differentiation. We propose that FGF-independent MEK1/2 signalling via an unknown ligand(s) also promotes Sertoli cell proliferation and organisation to indirectly facilitate male germline development