Kotov Alexei A, Olenkina Oxana M, Godneeva Baira K, Adashev Vladimir E, Olenina Ludmila V
Laboratory of Biochemical Genetics of Animals, Institute of Molecular Genetics, Russian Academy of Sciences.
Biosci Trends. 2017 Mar 22;11(1):46-53. doi: 10.5582/bst.2016.01216. Epub 2017 Feb 12.
Human DDX3 paralogs are housed on the X chromosome (DDX3X) as well as in the non- recombining region Yq11 of the Y-chromosome (DDX3Y or DBY). A gene encoding RNA helicase DDX3Y is located in the AZoospermia Factor a (AZFa) region of the Y-chromosome and expressed only in male germ cells. Deletions encompassing the DDX3Y gene lead to azoospermia and cause Sertoli Cell-Only Syndrome (SCOS) in humans. SCOS is characterized by a complete germ cell lack with preservation of somatic Sertoli cells. This review summarizes current advances in the study of DDX3Y functions in maintenance and development of early male germ cells. Data obtained from a mouse xenotransplantation model reveals that DDX3Y expression is enough to drive germ cell differentiation of AZFa-deleted human induced pluripotent stem cells (iPSCs) and for activation of the specific set of germline developmental genes. Results achieved using the testes of Drosophila demonstrate that DDX3Y homolog Belle is required cell-autonomously for mitotic progression and survival of germline stem cells and spermatogonia as the upstream regulator of mitotic cyclin expression.
人类DDX3旁系同源基因位于X染色体上（DDX3X），也存在于Y染色体的非重组区域Yq11（DDX3Y或DBY）。编码RNA解旋酶DDX3Y的基因位于Y染色体的无精子症因子a（AZFa）区域，仅在雄性生殖细胞中表达。包含DDX3Y基因的缺失会导致无精子症，并在人类中引起唯支持细胞综合征（SCOS）。SCOS的特征是完全缺乏生殖细胞，而体细胞支持细胞得以保留。本综述总结了DDX3Y在早期雄性生殖细胞维持和发育中的功能研究的当前进展。从小鼠异种移植模型获得的数据表明，DDX3Y的表达足以驱动AZFa缺失的人类诱导多能干细胞（iPSC）的生殖细胞分化，并激活特定的生殖系发育基因集。使用果蝇睾丸获得的结果表明，DDX3Y的同源物Belle作为有丝分裂周期蛋白表达的上游调节因子，对于生殖系干细胞和精原细胞的有丝分裂进程和存活是细胞自主必需的。
