A novel transcriptional factor Nkapl is a germ cell-specific suppressor of Notch signaling and is indispensable for spermatogenesis.
A novel transcriptional factor Nkapl is a germ cell-specific suppressor of Notch signaling and is indispensable for spermatogenesis.
复制标题
DOI：
10.1371/journal.pone.0124293
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tanaka H
中科院分区：
文献类型：
--
作者：
Okuda H;Kiuchi H;Takao T;Miyagawa Y;Tsujimura A;Nonomura N;Miyata H;Okabe M;Ikawa M;Kawakami Y;Goshima N;Wada M;Tanaka H
精子发生是一个精细调控的系统，致力于通过精原细胞的发生持续产生精子。在这个过程中，各种基因的表达是相关的生殖细胞在每个阶段的分化。尽管Notch信号在果蝇和秀丽隐杆线虫的生殖细胞发育中起着关键作用，但其在哺乳动物精子发生中的功能和重要性仍存在争议。我们报告Nkapl是一种新的生殖细胞特异性转录抑制Notch信号。它还与Notch辅阻遏物复合物的几种分子如CIR、HDAC3和CSL相关。3周龄后在精原细胞和早期精母细胞中表达。Nkapl缺失的小鼠在粗线期精母细胞水平上表现出完全停滞。此外，在该细胞类型中观察到细胞凋亡。NKAPL在生殖系干细胞中的过表达表明，Nkapl通过Notch信号通路诱导精原干细胞（SSC）标志物的变化和分化因子的减少，而Nkapl缺失的睾丸显示这些标志物和因子的相反变化。因此，Nkapl是必不可少的，因为异常升高的Notch信号传导对精子发生具有负面影响，影响SSC维持和分化因子。Notch信号转导应通过转录因子Nkapl适当调节。
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.
登录
查看更多内容
影响因子：
4.6
作者：
Kageyama, Ryoichiro;Ohtsuka, Toshiyuki;Kobayashi, Taeko
通讯作者：
Kobayashi, Taeko
影响因子：
2.5
作者：
Mori, S;Kadokawa, Y;Marunouchi, T
通讯作者：
Marunouchi, T
影响因子：
4.4
作者：
Michie, Alison M.;Chan, Angela C.;Izon, David J.
通讯作者：
Izon, David J.
DOI：
10.1073/pnas.0807297105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Anderson, Ericka L.;Baltus, Andrew E.;Page, David C.
通讯作者：
Page, David C.
DOI：
10.1073/pnas.1003462107
发表时间：
2010-08-10
影响因子：
11.1
作者：
Kitadate, Yu;Kobayashi, Satoru
通讯作者：
Kobayashi, Satoru