Fig. 4. Control of spermatogonial stem cell differentiation and self-renewal by GDNF dosage. GDNF is expressed by the Sertoli cells in the seminiferous tubules. These cells control sperm differentiation in a paracrine manner. When the GDNF level is low, the spermatogenic stem cells enter the differentiation pathway. When its level is high, the stem cells only self-renew and are unable to differentiate. In transgenic mice with loss- and gain-of-function of GDNF, both conditions lead to disturbed spermatogenesis.