日本研究人員日前報告說，他們發(fā)現(xiàn)在雄性果蠅體內存在一種調節(jié)機制,，可以通過有效增加精原干細胞來避免不育,。這一發(fā)現(xiàn)有望給不育病理和療法研究提供新思路。
日本基礎生物學研究所教授小林悟領導的研究小組發(fā)現(xiàn),，在雄性果蠅精巢前端的精原干細胞微環(huán)境中,，存在一種特殊細胞，只有與它們鄰近的原始生殖細胞,，才能發(fā)育成精原干細胞,，進而發(fā)展為精子。研究人員將這種特殊細胞稱為“鄰近細胞”。研究人員還發(fā)現(xiàn),，果蠅體內既存在使“鄰近細胞”增多的基因——notch基因,，也存在使“鄰近細胞”減少的基因——EGFR基因。在通常狀態(tài)下,，這兩種基因在精巢內“勢均力敵”,，從而保證制造出一定數(shù)量的“鄰近細胞”和精原干細胞。
如果因為疾病等意外,，原始生殖細胞數(shù)目顯著減少,，那么減少“鄰近細胞”的EGFR基因就會受到遏制，而使“鄰近細胞”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胞發(fā)育成精原干細胞,。這樣，即使只利用少數(shù)原始生殖細胞也能制造出較充足的精原干細胞,。但如果在原始生殖細胞顯著減少的情況下,，通過操作避免減少“鄰近細胞”的EGFR基因受到遏制，精原干細胞的生成就會日益萎靡,，從而導致不育,。
此次研究揭示了果蠅體內存在巧妙的調節(jié)機制，在其原始生殖細胞數(shù)目出現(xiàn)異常的情況下,，也能避免不育,。研究人員認為，這一研究可能有助于揭示其他動物避免不育的機制,，為研究精巢以外器官中的干細胞及其“鄰近細胞”間的調節(jié)機制提供線索,，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《國家科學院學報》(PNAS)網絡版上(藍建中),。(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.
