First Author | Mori Y | Year | 2021 |
Journal | Cell Rep | Volume | 36 |
Issue | 7 | Pages | 109550 |
PubMed ID | 34407418 | Mgi Jnum | J:310652 |
Mgi Id | MGI:6764037 | Doi | 10.1016/j.celrep.2021.109550 |
Citation | Mori Y, et al. (2021) Cdc42 is required for male germline niche development in mice. Cell Rep 36(7):109550 |
abstractText | Spermatogonial stem cells (SSCs) are maintained in a special microenvironment called a niche. However, much is unknown about components that constitute the niche. Here, we report that Cdc42 is essential for germline niche development. Sertoli cell-specific Cdc42-deficient mice showed normal premeiotic spermatogenesis. However, germ cells gradually disappeared during haploid cell formation and few germ cells remained in the mature testes. Spermatogonial transplantation experiments revealed a significant loss of SSCs in Cdc42-deficient testes. Moreover, Cdc42 deficiency in Sertoli cells downregulated GDNF, a critical factor for SSC maintenance. Cdc42-deficient Sertoli cells also exhibited lower nuclear MAPK1/3 staining. Inhibition of MAP2K1 or depletion of Pea15a scaffold protein downregulated GDNF expression. A screen of transcription factors revealed that Cdc42-deficient Sertoli cells downregulate DMRT1 and SOX9, both of which are critical for Sertoli cell development. These results indicate that Cdc42 is essential for niche function via MAPK1/3-dependent GDNF secretion. |