Song Xiaoqing, Wong Marco D, Kawase Eihachiro, Xi Rongwen, Ding Bee C, McCarthy John J, Xie Ting
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Development. 2004 Mar;131(6):1353-64. doi: 10.1242/dev.01026. Epub 2004 Feb 18.
The Drosophila ovary is an attractive system to study how niches control stem cell self-renewal and differentiation. The niche for germline stem cells (GSCs) provides a Dpp/Bmp signal, which is essential for GSC maintenance. bam is both necessary and sufficient for the differentiation of immediate GSC daughters, cystoblasts. Here we show that Bmp signals directly repress bam transcription in GSCs in the Drosophila ovary. Similar to dpp, gbb encodes another Bmp niche signal that is essential for maintaining GSCs. The expression of phosphorylated Mad (pMad), a Bmp signaling indicator, is restricted to GSCs and some cystoblasts, which have repressed bam expression. Both Dpp and Gbb signals contribute to pMad production. bam transcription is upregulated in GSCs mutant for dpp and gbb. In marked GSCs mutant for Med and punt, two essential Bmp signal transducers, bam transcription is also elevated. Finally, we show that Med and Mad directly bind to the bam silencer in vitro. This study demonstrates that Bmp signals maintain the undifferentiated or self-renewal state of GSCs, and directly repress bam expression in GSCs by functioning as short-range signals. Thus, niche signals directly repress differentiation-promoting genes in stem cells in order to maintain stem cell self-renewal.
果蝇卵巢是研究微环境如何控制干细胞自我更新和分化的一个有吸引力的系统。生殖系干细胞（GSCs）的微环境提供了一种Dpp/Bmp信号，这对于GSC的维持至关重要。bam对于紧邻GSC的子代细胞即成囊细胞的分化既是必要的也是充分的。在这里我们表明，Bmp信号在果蝇卵巢的GSCs中直接抑制bam转录。与dpp类似，gbb编码另一种对维持GSCs至关重要的Bmp微环境信号。磷酸化的Mad（pMad）作为一种Bmp信号指示物，其表达局限于已抑制bam表达的GSCs和一些成囊细胞。Dpp和Gbb信号都有助于pMad的产生。在dpp和gbb突变的GSCs中，bam转录上调。在Med和punt这两个重要的Bmp信号转导因子突变的标记GSCs中，bam转录也升高。最后，我们表明Med和Mad在体外直接结合到bam沉默子上。这项研究表明，Bmp信号维持GSCs的未分化或自我更新状态，并通过作为短程信号发挥作用，直接在GSCs中抑制bam表达。因此，微环境信号直接抑制干细胞中促进分化的基因，以维持干细胞的自我更新。
