Distinct Roles for Rac1 in Sertoli Cell Function during Testicular Development and Spermatogenesis
Distinct Roles for Rac1 in Sertoli Cell Function during Testicular Development and Spermatogenesis
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DOI：
10.1016/j.celrep.2020.03.077
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发表时间：
2020-04-14
期刊：
影响因子：
8.8
通讯作者：
DeFalco, Tony
中科院分区：
文献类型：
--
作者：
Heinrich, Anna;Potter, Sarah J.;DeFalco, Tony
支持细胞是睾丸生精小管的支持细胞，为精子发生提供了一个滋养环境。成年支持细胞被极化，使得它们可以同时支持早期生精细胞（例如，精原细胞）基底和后期细胞（例如，精子细胞）顶部。为了测试破坏支持细胞极性的后果，我们进行了支持细胞特异性的Rac 1的条件性缺失，Rac 1编码顶基底细胞极性所需的Rho GT3。Rac1条件性基因敲除的成年人在圆形精子细胞阶段表现出生精停滞，支持细胞极性严重破坏，并表现出生殖细胞和支持细胞凋亡增加。因此，Sertoli Rac 1功能对于精子发生的进展是至关重要的，但令人惊讶的是，对于胎儿睾丸发育、未分化精原细胞的成人维持和减数分裂进入是不可或缺的。我们的数据表明，Sertoli Rac1功能只需要在精子发生的某些方面，并揭示细胞分化过程中细胞极性有不同的要求。
Sertoli cells are supporting cells of the testicular seminiferous tubules, which provide a nurturing environment for spermatogenesis. Adult Sertoli cells are polarized so that they can simultaneously support earlier-stage spermatogenic cells (e.g., spermatogonia) basally and later-stage cells (e.g., spermatids) apically. To test the consequences of disrupting cell polarity in Sertoli cells, we perform a Sertoli-specific conditional deletion of Rac1, which encodes a Rho GTPase required for apicobasal cell polarity. Rac1 conditional knockout adults exhibit spermatogenic arrest at the round spermatid stage, with severe disruption of Sertoli cell polarity, and show increased germline and Sertoli cell apoptosis. Thus, Sertoli Rac1 function is critical for the progression of spermatogenesis but, surprisingly, is dispensable for fetal testicular development, adult maintenance of undifferentiated spermatogonia, and meiotic entry. Our data indicate that Sertoli Rac1 function is required only for certain aspects of spermatogenesis and reveal that there are distinct requirements for cell polarity during cellular differentiation.