Hayashi Yoshiki, Kobayashi Satoru, Nakato Hiroshi
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
J Cell Biol. 2009 Nov 16;187(4):473-80. doi: 10.1083/jcb.200904118. Epub 2009 Nov 9.
Stem cells are maintained in vivo by short-range signaling systems in specialized microenvironments called niches, but the molecular mechanisms controlling the physical space of the stem cell niche are poorly understood. In this study, we report that heparan sulfate (HS) proteoglycans (HSPGs) are essential regulators of the germline stem cell (GSC) niches in the Drosophila melanogaster gonads. GSCs were lost in both male and female gonads of mutants deficient for HS biosynthesis. dally, a Drosophila glypican, is expressed in the female GSC niche cells and is responsible for maintaining the GSC niche. Ectopic expression of dally in the ovary expanded the niche area, showing that dally is required for restriction of the GSC niche space. Interestingly, the other glypican, dally-like, plays a major role in regulating male GSC niche maintenance. We propose that HSPGs define the physical space of the niche by serving as trans coreceptors, mediating short-range signaling by secreted factors.
干细胞在体内由称为龛位的特殊微环境中的短程信号系统维持,但控制干细胞龛位物理空间的分子机制仍知之甚少。在本研究中,我们报道硫酸乙酰肝素(HS)蛋白聚糖(HSPG)是果蝇性腺中生殖系干细胞(GSC)龛位的重要调节因子。在HS生物合成缺陷的突变体的雄性和雌性性腺中,GSC均缺失。dally是一种果蝇糖基磷脂酰肌醇锚定蛋白聚糖,在雌性GSC龛位细胞中表达,负责维持GSC龛位。卵巢中dally的异位表达扩大了龛位区域,表明dally是限制GSC龛位空间所必需的。有趣的是,另一种糖基磷脂酰肌醇锚定蛋白聚糖dally样蛋白在调节雄性GSC龛位维持中起主要作用。我们提出,HSPG通过作为跨共受体来定义龛位的物理空间,介导分泌因子的短程信号传导。