| First Author | Gustin SE | Year | 2016 |
| Journal | Reproduction | Volume | 152 |
| Issue | 5 | Pages | 529-43 |
| PubMed ID | 27495231 | Mgi Jnum | J:237045 |
| Mgi Id | MGI:5810810 | Doi | 10.1530/REP-16-0293 |
| Citation | Gustin SE, et al. (2016) FGF9, activin and TGFbeta promote testicular characteristics in an XX gonad organ culture model. Reproduction 152(5):529-43 |
| abstractText | Testis development is dependent on the key sex-determining factors SRY and SOX9, which activate the essential ligand FGF9. Although FGF9 plays a central role in testis development, it is unable to induce testis formation on its own. However, other growth factors, including activins and TGFbetas, also present testis during testis formation. In this study, we investigated the potential of FGF9 combined with activin and TGFbeta to induce testis development in cultured XX gonads. Our data demonstrated differing individual and combined abilities of FGF9, activin and TGFbeta to promote supporting cell proliferation, Sertoli cell development and male germ line differentiation in cultured XX gonads. FGF9 promoted proliferation of supporting cells in XX foetal gonads at rates similar to those observed in vivo during testis cord formation in XY gonads but was insufficient to initiate testis development. However, when FGF9, activin and TGFbeta were combined, aspects of testicular development were induced, including the expression of Sox9, morphological reorganisation of the gonad and deposition of laminin around germ cells. Enhancing beta-catenin activity diminished the testis-promoting activities of the combined growth factors. The male promoting activity of FGF9 and the combined growth factors directly or indirectly extended to the germ line, in which a mixed phenotype was observed. FGF9 and the combined growth factors promoted male germ line development, including mitotic arrest, but expression of pluripotency genes was maintained, rather than being repressed. Together, our data provide evidence that combined signalling by FGF9, activin and TGFbeta can induce testicular characteristics in XX gonads. |
