| First Author | Lu C | Year | 2022 |
| Journal | Development | Volume | 149 |
| Issue | 13 | PubMed ID | 35698877 |
| Mgi Jnum | J:361544 | Mgi Id | MGI:7377803 |
| Doi | 10.1242/dev.200205 | Citation | Lu C, et al. (2022) Casein kinase 1alpha regulates murine spermatogenesis via p53-Sox3 signaling. Development 149(13):dev200205 |
| abstractText | Casein kinase 1alpha (CK1alpha), acting as one member of the beta-catenin degradation complex, negatively regulates the Wnt/beta-catenin signaling pathway. CK1alpha knockout usually causes both Wnt/beta-catenin and p53 activation. Our results demonstrated that conditional disruption of CK1alpha in spermatogonia impaired spermatogenesis and resulted in male mouse infertility. The progenitor cell population was dramatically decreased in CK1alpha conditional knockout (cKO) mice, while the proliferation of spermatogonial stem cells (SSCs) was not affected. Furthermore, our molecular analyses identified that CK1alpha loss was accompanied by nuclear stability of p53 protein in mouse spermatogonia, and dual-luciferase reporter and chromatin immunoprecipitation assays revealed that p53 directly targeted the Sox3 gene. In addition, the p53 inhibitor pifithrin alpha (PFTalpha) partially rescued the phenotype observed in cKO mice. Collectively, our data suggest that CK1alpha regulates spermatogenesis and male fertility through p53-Sox3 signaling, and they deepen our understanding of the regulatory mechanism underlying the male reproductive system. |
