日本研究人員日前報(bào)告說,，他們發(fā)現(xiàn)在雄性果蠅體內(nèi)存在一種調(diào)節(jié)機(jī)制，可以通過有效增加精原干細(xì)胞來避免不育,。這一發(fā)現(xiàn)有望給不育病理和療法研究提供新思路,。
日本基礎(chǔ)生物學(xué)研究所教授小林悟領(lǐng)導(dǎo)的研究小組發(fā)現(xiàn)，在雄性果蠅精巢前端的精原干細(xì)胞微環(huán)境中,，存在一種特殊細(xì)胞,，只有與它們鄰近的原始生殖細(xì)胞，才能發(fā)育成精原干細(xì)胞,，進(jìn)而發(fā)展為精子,。研究人員將這種特殊細(xì)胞稱為“鄰近細(xì)胞”。研究人員還發(fā)現(xiàn),，果蠅體內(nèi)既存在使“鄰近細(xì)胞”增多的基因——notch基因,，也存在使“鄰近細(xì)胞”減少的基因——EGFR基因,。在通常狀態(tài)下,，這兩種基因在精巢內(nèi)“勢均力敵”，從而保證制造出一定數(shù)量的“鄰近細(xì)胞”和精原干細(xì)胞,。
如果因?yàn)榧膊〉纫馔?，原始生殖?xì)胞數(shù)目顯著減少，那么減少“鄰近細(xì)胞”的EGFR基因就會(huì)受到遏制,，而使“鄰近細(xì)胞”增加的notch基因則更加積極地發(fā)揮作用,，從而幫助原始生殖細(xì)胞發(fā)育成精原干細(xì)胞。這樣,，即使只利用少數(shù)原始生殖細(xì)胞也能制造出較充足的精原干細(xì)胞,。但如果在原始生殖細(xì)胞顯著減少的情況下，通過操作避免減少“鄰近細(xì)胞”的EGFR基因受到遏制,，精原干細(xì)胞的生成就會(huì)日益萎靡,，從而導(dǎo)致不育。
此次研究揭示了果蠅體內(nèi)存在巧妙的調(diào)節(jié)機(jī)制，在其原始生殖細(xì)胞數(shù)目出現(xiàn)異常的情況下,，也能避免不育,。研究人員認(rèn)為，這一研究可能有助于揭示其他動(dòng)物避免不育的機(jī)制,，為研究精巢以外器官中的干細(xì)胞及其“鄰近細(xì)胞”間的調(diào)節(jié)機(jī)制提供線索,，并有望給人類不育療法研究提供新思路。該研究成果將刊登在本周的美國《國家科學(xué)院學(xué)報(bào)》(PNAS)網(wǎng)絡(luò)版上(藍(lán)建中),。(生物谷Bioon.com)
生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.1003462107
Notch and Egfr signaling act antagonistically to regulate germ-line stem cell niche formation in Drosophila male embryonic gonads
Yu Kitadatea,b and Satoru Kobayashia,b,1
a Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, Higashiyama, Myodaiji, Okazaki 444-8787, Japan; and
b Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies, Nishigonaka, Myodaiji, Okazaki 444-8585, Japan
Germ-line stem cells (GSCs) are maintained by the somatic microenvironment, or GSC niche, which ensures that GSCs can both self-renew and produce functional gametes. However, it remains unclear how the proper niche size and location are regulated within the developing gonads. In the Drosophila testis, the hub cells that form the GSC niche are derived from a subset of somatic gonadal precursors (SGPs) in the anterior portion of the embryonic gonad. Here we show that Notch signaling induces hub differentiation. Notch is activated in almost all SGPs in the male embryonic gonad, but Epidermal growth factor receptor (Egfr) is activated in posterior SGPs to repress hub differentiation, thereby restricting the expansion of hub differentiation in the embryonic gonad. We further show that Egfr is activated in posterior SGPs by Spitz ligand secreted from primordial germ cells (PGCs), whereas the Notch ligand Serrate is expressed in SGPs. This suggests that varying the number of PGCs alters niche size. Indeed, a decrease in the number of PGCs causes ectopic hub differentiation, which consequently increases their opportunity to recruit PGCs as GSCs. When ectopic hub differentiation is repressed, the decreased number of PGCs fails to become GSCs. Thus, we propose that SGPs sense PGC number via signals from PGCs to SGPs that modulate niche size, and that this serves as a mechanism for securing GSCs.
