Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
PLoS Biol. 2011 Nov;9(11):e1001202. doi: 10.1371/journal.pbio.1001202. Epub 2011 Nov 22.
Stem cells and their niches constitute units that act cooperatively to achieve adult body homeostasis. How such units form and whether stem cell and niche precursors might be coordinated already during organogenesis are unknown. In fruit flies, primordial germ cells (PGCs), the precursors of germ line stem cells (GSCs), and somatic niche precursors develop within the larval ovary. Together they form the 16-20 GSC units of the adult ovary. We show that ecdysone receptors are required to coordinate the development of niche and GSC precursors. At early third instar, ecdysone receptors repress precocious differentiation of both niches and PGCs. Early repression is required for correct morphogenesis of the ovary and for protecting future GSCs from differentiation. At mid-third instar, ecdysone signaling is required for niche formation. Finally, and concurrent with the initiation of wandering behavior, ecdysone signaling initiates PGC differentiation by allowing the expression of the differentiation gene bag of marbles in PGCs that are not protected by the newly formed niches. All the ovarian functions of ecdysone receptors are mediated through early repression, and late activation, of the ecdysone target gene broad. These results show that, similar to mammals, a brain-gland-gonad axis controls the initiation of oogenesis in insects. They further exemplify how a physiological cue coordinates the formation of a stem cell unit within an organ: it is required for niche establishment and to ensure that precursor cells to adult stem cells remain undifferentiated until the niches can accommodate them. Similar principles might govern the formation of additional stem cell units during organogenesis.
干细胞及其所在的微环境构成了协同作用的单位,以实现成体的体内平衡。这些单位是如何形成的,以及干细胞和微环境前体细胞是否在器官发生过程中已经协调,目前尚不清楚。在果蝇中,原始生殖细胞(PGCs)是生殖干细胞(GSCs)的前体细胞,以及体细胞微环境前体细胞在幼虫卵巢中发育。它们共同形成成年卵巢的 16-20 个 GSC 单位。我们发现蜕皮激素受体对于协调微环境和 GSC 前体细胞的发育是必需的。在早期的第三龄期,蜕皮激素受体抑制微环境和 PGCs 的过早分化。早期的抑制对于卵巢的正确形态发生和保护未来的 GSCs 免受分化是必需的。在第三龄中期,蜕皮激素信号对于微环境的形成是必需的。最后,与游走行为的开始同时,蜕皮激素信号通过允许分化基因 bag of marbles 在不受新形成的微环境保护的 PGCs 中表达,启动 PGC 的分化。蜕皮激素受体的所有卵巢功能都是通过早期抑制和晚期激活蜕皮激素靶基因 broad 来介导的。这些结果表明,与哺乳动物类似,脑-腺体-性腺轴控制着昆虫卵发生的启动。它们进一步说明了生理信号如何协调器官内干细胞单位的形成:它对于微环境的建立是必需的,并确保前体细胞在微环境能够容纳它们之前保持未分化状态。类似的原则可能支配着器官发生过程中额外的干细胞单位的形成。