Kotov Alexei A, Olenkina Oxana M, Kibanov Mikhail V, Olenina Ludmila V
Laboratory of Biochemical Genetics of Animals, Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov Sq. 2, Moscow 123182, Russia.
Laboratory of Biochemical Genetics of Animals, Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov Sq. 2, Moscow 123182, Russia.
Biochim Biophys Acta. 2016 Jun;1863(6 Pt A):1093-105. doi: 10.1016/j.bbamcr.2016.02.006. Epub 2016 Feb 10.
The present study showed that RNA helicase Belle (DDX3) was required intrinsically for mitotic progression and survival of germline stem cells (GSCs) and spermatogonial cells in the Drosophila melanogaster testes. We found that deficiency of Belle in the male germline resulted in a strong germ cell loss phenotype. Early germ cells are lost through cell death, whereas somatic hub and cyst cell populations are maintained. The observed phenotype is related to that of the human Sertoli Cell-Only Syndrome caused by the loss of DBY (DDX3) expression in the human testes and results in a complete lack of germ cells with preservation of somatic Sertoli cells. We found the hallmarks of mitotic G2 delay in early germ cells of the larval testes of bel mutants. Both mitotic cyclins, A and B, are markedly reduced in the gonads of bel mutants. Transcription levels of cycB and cycA decrease significantly in the testes of hypomorph bel mutants. Overexpression of Cyclin B in the germline partially rescues germ cell survival, mitotic progression and fertility in the bel-RNAi knockdown testes. Taken together, these results suggest that a role of Belle in GSC maintenance and regulation of early germ cell divisions is associated with the expression control of mitotic cyclins.
本研究表明，RNA解旋酶Belle（DDX3）对于黑腹果蝇睾丸中生殖系干细胞（GSCs）和精原细胞的有丝分裂进程及存活至关重要。我们发现雄性生殖系中Belle的缺失会导致强烈的生殖细胞丢失表型。早期生殖细胞通过细胞死亡而丢失，而体细胞中心和包囊细胞群体得以维持。观察到的表型与人类睾丸中因DBY（DDX3）表达缺失导致的唯支持细胞综合征相关，该综合征会导致完全缺乏生殖细胞而体细胞支持细胞得以保留。我们在bel突变体幼虫睾丸的早期生殖细胞中发现了有丝分裂G2期延迟的特征。在bel突变体的性腺中，有丝分裂周期蛋白A和B均显著减少。在低表达bel突变体的睾丸中，cycB和cycA的转录水平显著降低。在生殖系中过表达细胞周期蛋白B可部分挽救bel-RNAi敲低睾丸中的生殖细胞存活、有丝分裂进程和生育能力。综上所述，这些结果表明Belle在GSC维持和早期生殖细胞分裂调控中的作用与有丝分裂周期蛋白的表达控制有关。
