Mammalian Development Laboratory・Saga Group

In the mouse, testicular development is triggered in somatic cells by the function of Sry followed by the activation of fibroblast growth factor (FGF) 9, which regulates testicular differentiation in both somatic and germ cells. However, the mechanism is unknown. We show here that Nodal/Activin signaling pathway is activated in both male gem cells and somatic cells. The disruption of Nodal/Activin signaling drives male germ cells into meiosis and causes ectopic initiation of female-specific genes in somatic cells.
Furthermore, we prove that Nodal/Activin-A works directly on male germ cells to induce male specific gene, Nanos2 independently of FGF9. We conclude that Nodal/Activin signaling is required for testicular development and propose a model in which Nodal/Activin-A acts downstream of FGF signaling to promote male germ cell fate and protect somatic cells from initiating female differentiation.

This study is conducted by Quan Wu who is a current student of SOKENDAI.

A model proposed by our study. FGF signals activate Nodal/Activin signaling pathway in both somatic cells and germ cells. Nodal/Activin-A triggers male sex differentiation by inducing male-specific genes, Nanos2 and Dnmt3L. Meanwhile, it suppresses Stra8 that is an essential gatekeeper of meiosis. In somatic cells Nodal/Activin-A thwarts the process of female differentiation by inhibiting Bmp2 and Follistatin.