Study On CDK2and CDK2Activation Regulated Meiotic Progression In Mice

Spermatogenesis is a complex process of reproduction cells differentiation. Spermatogenesis is characterized by three specific functional phases:spermatogonial proliferation, meiosis, and metamorphosis. In the proliferation phase, spermatogonia undergo several mitotic divisions to form spermatocytes which undergo two meiotic divisions to form haploid spermatids. Spermatogenesis constitutes undifferentiated spermatogonial renewal and proliferation, spermatogonial differentiation, meiosis of spermatocytes, and metamorphosis of spermatids. In most organisms, Meiosis I is a special process. The relevant processes include alignment of homologs, assembly of the synaptonemal complex (SC), genetic recombination, and the formation of chiasmata. The above processes are abnormal to evoke meiotic arrest and spermatogenesis disorder resulting in sterility. Telomere clustering is a widespread phenomenon among eukaryotes. However, the molecular mechanisms that regulate formation and dispersion of telomere clustering in chromosome pairing, recombination, and segregation, especially in mammals, are still largely unknown. Here we show that CDK2(Cyclin-dependent kinase2), especially p39cdk2, as a potential meiosis-specific connector interaction with SUN1mediates formation of telomere clustering during meiosis in mice, but transition from CDK2to p-CDK2(phosphorylation-CDK2) regulates dispersion of telomere clustering from late pachytene to diplotene. Further results suggested CDK2disappeared on the ends of SCP3(forming ring chromosome) and dispersed in the nucleus in Sunl-/-mice. In addition, we found that the spatiotemporal expression patterns of foci containing CDK2/MLH1compared to those containing p-CDK2/MLH1matched the progression from homologous recombination to desynapsis. However, the labeling pattern of p-CDK2disappeared at recombination sites in pachytene-arrested hybrid sterile mice (pwk×c57BL/6F1), and intensively distributed at unpaired chromosomal regions to regulate pachytene progression. These results suggest that transition from CDK2to p-CDK2plays a critical role for regulating meiosis progression.