The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis
The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis
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DOI：
10.1242/dev.193862
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发表时间：
2020-11-01
期刊：
影响因子：
4.6
通讯作者：
Ward, Jordan D.
中科院分区：
文献类型：
--
作者：
Ragle, James Matthew;Aita, Abigail L.;Ward, Jordan D.
在有性生殖的后生动物中，精子发生是未定型生殖细胞产生单倍体精子的过程。模型系统的工作揭示了控制精子命运的机制，但这种命运随后如何执行仍不清楚。在研究保守的核激素受体转录因子 NHR-23/NR1F1 在调节线虫蜕皮中的既定作用时，我们发现 NHR-23/NR1F1 在发育中的初级精母细胞中也组成型表达，并且是精子发生的关键调节因子。在这一新角色中，NHR-23/NR1F1 在经典性别决定途径的下游发挥作用。雌雄同体或雄性种系中由 Degron 介导的 NHR-23/NR1F1 耗竭会导致不育，因为缺乏功能性精子，因为耗竭的动物会产生停滞的初级精母细胞而不是单倍体精子。这些精母细胞停滞在前中期 I，并且无法进展到后期或尝试精子细胞残余体分配。它们制造精子特异性的膜细胞器，但无法将主要的精子蛋白组装成纤维体。 NHR-23/NR1F1 的功能似乎独立于已知的 SPE-44 基因调控网络，揭示了 NHR-23/NR1F1 介导的调节精子发生程序的模块的存在。
In sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulating C. elegans molting, we discovered that NHR-23/NR1F1 is also constitutively expressed in developing primary spermatocytes and is a critical regulator of spermatogenesis. In this novel role, NHR-23/NR1F1 functions downstream of the canonical sex-determination pathway. Degron-mediated depletion of NHR-23/NR1F1 within hermaphrodite or male germlines causes sterility due to an absence of functional sperm, as depleted animals produce arrested primary spermatocytes rather than haploid sperm. These spermatocytes arrest in prometaphase I and fail to either progress to anaphase or attempt spermatid-residual body partitioning. They make sperm-specific membranous organelles but fail to assemble their major sperm protein into fibrous bodies. NHR-23/NR1F1 appears to function independently of the known SPE-44 gene regulatory network, revealing the existence of an NHR-23/NR1F1-mediated module that regulates the spermatogenesis program.