Guo Zheng, Wang Zhaohui
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beichen Xilu #1, Beijing 100101, P.R. China.
Development. 2009 Nov;136(21):3627-35. doi: 10.1242/dev.036939. Epub 2009 Sep 30.
The Drosophila ovary is an excellent system with which to study germline stem cell (GSC) biology. Two or three female GSCs are maintained in a structure called a niche at the anterior tip of the ovary. The somatic niche cells surrounding the GSCs include terminal filament cells, cap cells and escort stem cells. Mounting evidence has demonstrated that BMP-like morphogens are the immediate upstream signals to promote GSC fate by preventing the expression of Bam, a key differentiation factor. In contrast to their morphogenic long-range action in imaginal epithelia, BMP molecules in the ovarian niche specify GSC fate at single-cell resolution. How this steep gradient of BMP response is achieved remains elusive. In this study, we found that the glypican Dally is essential for maintaining GSC identity. Dally is highly expressed in cap cells. Cell-specific Dally-RNAi, mutant clonal analysis and cell-specific rescue of the GSC-loss phenotype suggest that Dally acts in the cap cells adjacent to the GSCs. We confirmed that Dally facilitated BMP signaling in GSCs by examining its downstream targets in various dally mutants. Conversely, when we overexpressed Dally in somatic cells outside the niche, we increased the number of GSC-like cells apparently by expanding the pro-GSC microenvironment. Furthermore, in a genetic setting we revealed a BMP-sensitivity distinction between germline and somatic cells, namely that Dally is required for short-range BMP signaling in germline but not in somatic cells. We propose that Dally ensures high-level BMP signaling in the ovarian niche and thus female GSC determination.
果蝇卵巢是研究生殖系干细胞（GSC）生物学的极佳系统。在卵巢前端的一个称为微环境的结构中维持着两到三个雌性生殖系干细胞。围绕生殖系干细胞的体细胞微环境细胞包括端丝细胞、帽细胞和护送干细胞。越来越多的证据表明，类骨形态发生蛋白（BMP）是通过抑制关键分化因子Bam的表达来促进生殖系干细胞命运的直接上游信号。与它们在成虫上皮细胞中的形态发生长距离作用相反，卵巢微环境中的BMP分子以单细胞分辨率决定生殖系干细胞的命运。这种陡峭的BMP反应梯度是如何实现的仍然不清楚。在这项研究中，我们发现硫酸乙酰肝素蛋白聚糖Dally对于维持生殖系干细胞的特性至关重要。Dally在帽细胞中高度表达。细胞特异性的Dally-RNA干扰、突变克隆分析以及生殖系干细胞丢失表型的细胞特异性挽救表明，Dally在与生殖系干细胞相邻的帽细胞中起作用。通过检查各种dally突变体中的下游靶点，我们证实Dally促进了生殖系干细胞中的BMP信号传导。相反，当我们在微环境外的体细胞中过表达Dally时，我们明显通过扩大前生殖系干细胞微环境增加了生殖系干细胞样细胞的数量。此外，在一个遗传学背景下，我们揭示了生殖细胞和体细胞之间对BMP敏感性的差异，即Dally是生殖细胞中短距离BMP信号传导所必需的，而在体细胞中则不是。我们提出，Dally确保了卵巢微环境中高水平的BMP信号传导，从而决定了雌性生殖系干细胞。
