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一种新型转录因子Nkapl是Notch信号通路的生殖细胞特异性抑制因子，对精子发生不可或缺。

A novel transcriptional factor Nkapl is a germ cell-specific suppressor of Notch signaling and is indispensable for spermatogenesis.

作者信息

Okuda Hidenobu, Kiuchi Hiroshi, Takao Tetsuya, Miyagawa Yasushi, Tsujimura Akira, Nonomura Norio, Miyata Haruhiko, Okabe Masaru, Ikawa Masahito, Kawakami Yoshitaka, Goshima Naoki, Wada Morimasa, Tanaka Hiromitsu

机构信息

Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.

Department of Urology, Juntendo University Hospital, Tokyo, Japan.

出版信息

PLoS One. 2015 Apr 14;10(4):e0124293. doi: 10.1371/journal.pone.0124293. eCollection 2015.

DOI:10.1371/journal.pone.0124293
PMID:25875095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4397068/
Abstract

Spermatogenesis is an elaborately regulated system dedicated to the continuous production of spermatozoa via the genesis of spermatogonia. In this process, a variety of genes are expressed that are relevant to the differentiation of germ cells at each stage. Although Notch signaling plays a critical role in germ cell development in Drosophila and Caenorhabditis elegans, its function and importance for spermatogenesis in mammals is controversial. We report that Nkapl is a novel germ cell-specific transcriptional suppressor in Notch signaling. It is also associated with several molecules of the Notch corepressor complex such as CIR, HDAC3, and CSL. It was expressed robustly in spermatogonia and early spermatocytes after the age of 3 weeks. Nkapl-deleted mice showed complete arrest at the level of pachytene spermatocytes. In addition, apoptosis was observed in this cell type. Overexpression of NKAPL in germline stem cells demonstrated that Nkapl induced changes in spermatogonial stem cell (SSC) markers and the reduction of differentiation factors through the Notch signaling pathway, whereas testes with Nkapl deleted showed inverse changes in those markers and factors. Therefore, Nkapl is indispensable because aberrantly elevated Notch signaling has negative effects on spermatogenesis, affecting SSC maintenance and differentiation factors. Notch signaling should be properly regulated through the transcriptional factor Nkapl.

摘要

精子发生是一个精心调控的系统，致力于通过精原细胞的发生持续产生精子。在这个过程中，会表达多种与各阶段生殖细胞分化相关的基因。尽管Notch信号通路在果蝇和秀丽隐杆线虫的生殖细胞发育中起关键作用，但其在哺乳动物精子发生中的功能和重要性仍存在争议。我们报道Nkapl是Notch信号通路中一种新的生殖细胞特异性转录抑制因子。它还与Notch共抑制复合物的几种分子相关，如CIR、HDAC3和CSL。它在3周龄后的精原细胞和早期精母细胞中大量表达。Nkapl基因敲除的小鼠在粗线期精母细胞阶段完全停滞。此外，在这种细胞类型中观察到了凋亡。在生殖系干细胞中过表达NKAPL表明，Nkapl通过Notch信号通路诱导精原干细胞（SSC）标志物的变化以及分化因子的减少，而Nkapl基因敲除的睾丸在这些标志物和因子上表现出相反的变化。因此，Nkapl是不可或缺的，因为Notch信号通路异常升高会对精子发生产生负面影响，影响SSC的维持和分化因子。Notch信号通路应通过转录因子Nkapl进行适当调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/f90c334b80a5/pone.0124293.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/1e29a9bd5127/pone.0124293.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/60bb202221e9/pone.0124293.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/eb90ba648fa4/pone.0124293.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/da07fa3456fc/pone.0124293.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/768b5ddd5767/pone.0124293.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/3a4aa973b797/pone.0124293.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/f90c334b80a5/pone.0124293.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/1e29a9bd5127/pone.0124293.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/60bb202221e9/pone.0124293.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/eb90ba648fa4/pone.0124293.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/da07fa3456fc/pone.0124293.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/768b5ddd5767/pone.0124293.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/3a4aa973b797/pone.0124293.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a05/4397068/f90c334b80a5/pone.0124293.g007.jpg

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