Press release

Press Release (Only in Japanese)

Evolutionally conserved Nanos RNA-binding proteins play crucial roles in germ cell development. While a mammalian Nanos family protein, NANOS2, is required for sexual differentiation of male (XY) germ cells in mice, the underlying mechanisms and the identities of its target RNAs in vivo remain elusive. Using comprehensive microarray analysis and a bacterial artificial chromosome transgenic system, we identify Dazl, a germ cell-specific gene encoding an RNA-binding protein implicated in translation, as a crucial target of NANOS2. Importantly, removal of the Dazl 3′ UTR in XY germ cells stabilises the Dazl mRNA, resulting in elevated meiotic gene expression, abnormal resumption of the cell cycle, and impaired processing-body formation, reminiscent of Nanos2-knockout phenotypes. Furthermore, our data suggest that NANOS2 acts as an antagonist of the DAZL protein. We propose a dual system of NANOS2-mediated suppression of Dazl expression as a pivotal molecular mechanism promoting sexual differentiation of XY germ cells. This work was supported by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JSPS) to Y.K. (Grant number 25840091) and a Grant-in-Aid for Scientific Research (S) from JSPS to Y.S. (Grant number 21227008).

(A)Sex of mouse germ cells is determined after they are enclosed by gonadal somatic cells at E11.5. NANOS2 expression begins once primordial germ cells enter the sex-specific process of sexual differentiation in male germ cells. Germ cells lacking the Nanos2 gene die by apoptosis due to the abrogated male-type differentiation.
(B)Working model of NANOS2-dependent Dazl suppression in sexually differentiating male germ cells.