日本研究人员日前报告说，他们发现在雄性果蝇体内存在一种调节机制，可以通过有效增加精原干细胞来避免不育。这一发现有望给不育病理和疗法研究提供新思路。
日本基础生物学研究所教授小林悟领导的研究小组发现，在雄性果蝇精巢前端的精原干细胞微环境中，存在一种特殊细胞，只有与它们邻近的原始生殖细胞，才能发育成精原干细胞，进而发展为精子。研究人员将这种特殊细胞称为“邻近细胞”。研究人员还发现，果蝇体内既存在使“邻近细胞”增多的基因――notch基因，也存在使“邻近细胞”减少的基因――EGFR基因。在通常状态下，这两种基因在精巢内“势均力敌”，从而保证制造出一定数量的“邻近细胞”和精原干细胞。
如果因为疾病等意外，原始生殖细胞数目显着减少，那么减少“邻近细胞”的EGFR基因就会受到遏制，而使“邻近细胞”增加的notch基因则更加积极地发挥作用，从而帮助原始生殖细胞发育成精原干细胞。这样，即使只利用少数原始生殖细胞也能制造出较充足的精原干细胞。但如果在原始生殖细胞显着减少的情况下，通过操作避免减少“邻近细胞”的EGFR基因受到遏制，精原干细胞的生成就会日益萎靡，从而导致不育。
此次研究揭示了果蝇体内存在巧妙的调节机制，在其原始生殖细胞数目出现异常的情况下，也能避免不育。研究人员认为，这一研究可能有助于揭示其他动物避免不育的机制，为研究精巢以外器官中的干细胞及其“邻近细胞”间的调节机制提供线索，并有望给人类不育疗法研究提供新思路。该研究成果将刊登在本周的美国《国家科学院学报》(PNAS)网络版上(蓝建中)。
推荐原文出处：
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.
