期刊
DEVELOPMENT
卷 140, 期 2, 页码 291-300出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.087882
关键词
Male germ cells; Nodal/activin signaling; Nanos2; Sex differentiation; Nodal conditional knockout; Smad4 conditional knockout; Mouse
资金
- Genome Network Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Japan Society for the Promotion of Science (JSPS) [KAKENHI] [21227008]
- Iwatani Naoji Foundation
- Intramural Program of the National Institutes of Health
- Grants-in-Aid for Scientific Research [21227008] Funding Source: KAKEN
Testicular development in the mouse is triggered in somatic cells by the function of Sry followed by the activation of fibroblast growth factor 9 (FGF9), which regulates testicular differentiation in both somatic and germ cells. However, the mechanism is unknown. We show here that the nodal/activin signaling pathway is activated in both male germ cells and somatic cells. 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 the 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 fibroblast growth factor signaling to promote male germ cell fate and protect somatic cells from initiating female differentiation.
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