Ohhara Yuya, Kobayashi Satoru, Yamanaka Naoki
Department of Entomology, Institute for Integrative Genome Biology, Center for Disease Vector Research, University of California, Riverside, Riverside, California, United States of America.
Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan.
PLoS Genet. 2017 Jan 25;13(1):e1006583. doi: 10.1371/journal.pgen.1006583. eCollection 2017 Jan.
Many animals have an intrinsic growth checkpoint during juvenile development, after which an irreversible decision is made to upregulate steroidogenesis, triggering the metamorphic juvenile-to-adult transition. However, a molecular process underlying such a critical developmental decision remains obscure. Here we show that nutrient-dependent endocycling in steroidogenic cells provides the machinery necessary for irreversible activation of metamorphosis in Drosophila melanogaster. Endocycle progression in cells of the prothoracic gland (PG) is tightly coupled with the growth checkpoint, and block of endocycle in PG cells causes larval developmental arrest due to reduction in biosynthesis of the steroid hormone ecdysone. Moreover, inhibition of the nutrient sensor target of rapamycin (TOR) in the PG during the checkpoint period causes endocycle inhibition and developmental arrest, which can be rescued by inducing additional rounds of endocycles by Cyclin E. We propose that a TOR-mediated cell cycle checkpoint in steroidogenic tissue provides a systemic growth checkpoint for reproductive maturation.
许多动物在幼体发育过程中存在一个内在的生长检查点，在此之后会做出上调类固醇生成的不可逆决定，从而触发从幼体到成体的变态转变。然而，这一关键发育决定背后的分子过程仍不清楚。在这里，我们表明，类固醇生成细胞中营养物质依赖的内循环为果蝇变态的不可逆激活提供了必要机制。前胸腺（PG）细胞中的内循环进程与生长检查点紧密相关，PG细胞内循环的阻断会因类固醇激素蜕皮激素生物合成减少而导致幼虫发育停滞。此外，在检查点期间抑制PG中的营养传感器雷帕霉素靶蛋白（TOR）会导致内循环抑制和发育停滞，而通过Cyclin E诱导额外的内循环可以挽救这种情况。我们提出，类固醇生成组织中TOR介导的细胞周期检查点为生殖成熟提供了一个全身性的生长检查点。
