RBFOX2缺失抑制雄性小鼠的减数分裂起始

Loss of RBFOX2 inhibits meiotic initiation in male mice

摘要:

减数分裂起始是配子发生的关键步骤。目前人们已经发现了一些减数分裂起始所必需的基因，但是对于该过程的调控基因及其作用机制还知之甚少。本实验室先前建立了精原干细胞（spermatogonial stem cells，SSCs）体外培养以及体外诱导减数分裂起始的技术体系，为更好地探究减数分裂起始调控基因及作用机理提供了良好的条件。实验室前期研究发现RNA结合蛋白RBFOX2可能调控减数分裂起始，然而RBFOX2在生殖细胞的减数分裂起始过程中的功能及作用机制还需深入研究。本研究利用慢病毒介导的转基因技术产生了RBFOX2敲降的精原干细胞系；发现RBFOX2敲降后，精原干细胞的自我更新、增殖以及分化未发生显著变化，但是减数分裂无法启动，分化型精原细胞发生明显凋亡。这一结果进一步显示了RNA结合蛋白在雄性动物减数分裂起始中的重要功能。

Abstract:

Meiotic initiation is a critical step in gametogenesis. Recently, some genes required for meiotic initiation have been identified. However, meiosis-initiating factors and the underlying mechanisms are far from being fully understood. We have established a long-term culture system of spermatogonial stem cells (SSCs) and an in vitro model of meiotic initiation using mouse SSCs. Our previous study revealed that the RNA-binding protein RBFOX2 may regulate meiotic initiation, but the role and the mechanism need to be further elucidated. In this study, we constructed RBFOX2 knockdown SSC lines by using lentivirus-mediated gene delivery method, and found that the knockdown SSCs underwent normal self-renewal, mitosis and differentiation. However, they were unable to initiate meiosis when treated with retinoic acid, and they underwent apoptosis. These results indicate that RBFOX2 plays an essential role in meiotic initiation of spermatogonia. This work provides new clues for understanding the functions of RNA-binding proteins in meiotic initiation.