C-elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline
C-elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline
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DOI：
10.1016/j.cub.2006.02.073
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发表时间：
2006-04-18
期刊：
影响因子：
9.2
通讯作者：
Rothman, JH
中科院分区：
文献类型：
--
作者：
Fukuyama, M;Rougvie, AE;Rothman, JH
将营养线索与发育程序联系起来的分子途径知之甚少。秀丽隐杆线虫幼体在食物供应之前处于休眠状态，称为“L1滞育”。然而，很少有人知道是什么信号转导途径介导的营养状况，以控制逮捕和启动胚后发育。我们报道C.线虫胚胎生殖系前体经历G2停滞，染色体浓缩，并在整个L1滞育期间保持停滞。肿瘤抑制因子β-18/PTEN的缺失绕过了这种阻滞，导致依赖于AGE-1/PI-3和AKT-1/PKB激酶的不适当的种系生长。β-18还调节长寿和幼虫形成所必需的胰岛素/IGF样途径。然而，受此途径抑制的fos-16/FoxO并不是L1滞育中生殖系停滞所必需的。因此，这些研究结果表明，在L1滞育的种系发育的静止是不是一个被动的营养剥夺的后果，而是积极维持的β-18通过一个途径不同的调节寿命和dauer形成。
The molecular pathways that link nutritional cues to developmental programs are poorly understood. Caenorhabditis elegans hatchlings arrest in a dormant state termed "L1 diapause" until food is supplied. However, little is known about what signal transduction pathways mediate nutritional status to control arrest and initiation of postembryonic development. We report that C. elegans embryonic germline precursors undergo G2 arrest with condensed chromosomes and remain arrested throughout L1 diapause. Loss of the DAF-18/PTEN tumor suppressor bypasses this arrest, resulting in inappropriate germline growth dependent on the AGE-1/PI-3 and AKT-1/PKB kinases. DAF-18 also regulates an insulin/IGF-like pathway essential for longevity and dauer larva formation. However, DAF-16/FoxO, which is repressed by this pathway, is not required for germline arrest in L1 diapause. Thus, these findings indicate that quiescence of germline development during L1 diapause is not a passive consequence of nutrient deprivation, but rather is actively maintained by DAF-18 through a pathway distinct from that which regulates longevity and dauer formation.