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Publication : Cdc42 is required for male germline niche development in mice.

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.
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