Identification of late larval stage developmental checkpoints in Caenorhabditis elegans regulated by insulin/IGF and steroid hormone signaling pathways.
Identification of late larval stage developmental checkpoints in Caenorhabditis elegans regulated by insulin/IGF and steroid hormone signaling pathways.
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鉴定由胰岛素/IGF和类固醇激素信号通路调节的秀丽隐杆线虫中幼虫晚期发育检查点。
DOI：
10.1371/journal.pgen.1004426
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发表时间：
2014-06
期刊：
影响因子：
4.5
通讯作者：
Sherwood DR
中科院分区：
文献类型：
--
作者：
Schindler AJ;Baugh LR;Sherwood DR
野生生物的发育需要不同的食物供应。在营养匮乏时期，发育可能会减慢或停止，直到情况改善。调节发育程序以应对营养不良的能力需要一种感知营养环境变化和限制组织生长的方法。生物体实现这种适应的机制尚不清楚。我们试图通过检查营养缺乏对秀丽隐杆线虫幼虫晚期（L3 和 L4）发育的影响来研究这个问题，这是一个广泛的组织生长和形态发生的时期。通过在不同时间将动物从食物中取出，我们在此表明，早期 L3 和早期 L4 阶段存在特定的检查点，可以系统地阻止不同组织和细胞过程的发育。这些检查点在蜕皮后和随后的蜕皮周期开始之前的每个幼虫阶段发生一次。 DAF-2 是胰岛素/胰岛素样生长因子受体，可调节 L3 和 L4 检查点的通过以响应营养。 FOXO 转录因子 DAF-16 是胰岛素样信号传导的主要靶标，在皮下组织（皮肤）中非自主地发挥细胞功能，在营养物质去除后阻止发育。 DAF-16 对 L3 和 L4 阶段进展的影响是由 DAF-9 介导的，DAF-9 是一种细胞色素 P450 直向同源物，参与线虫类固醇激素的产生。我们的结果确定了线虫生长的一种新模式，其中发育从一个检查点进展到下一个检查点。在每个检查点，营养条件决定动物是保持停滞状态还是继续发育到下一个检查点。野生生物经常面临长期食物匮乏的情况。这可能是由于季节性影响、领地丧失或捕食者与猎物比率的变化而发生的。在稀缺时期，生物体会进行适应以节省资源并延长生存时间。当发育过程中发生营养缺乏时，身体生长和成年成熟就会延迟。这些影响也在营养不良的个体中观察到，这些个体体型较小，进入青春期的年龄较晚。因营养缺乏而导致的发育停滞需要一种感知营养条件变化并协调整个生物体反应的方法。这是如何发生的尚不清楚。我们评估了线虫秀丽隐杆线虫对营养撤退的发育反应。通过在幼虫后期（广泛组织形成的时期）去除食物，我们发现了在发育的精确时间发生的先前未知的检查点。不同的组织和细胞过程在检查站停滞。胰岛素样信号传导和类固醇激素信号传导调节营养撤除后的组织停滞。这些途径在哺乳动物中是保守的，并且与生长过程和疾病有关。鉴于对营养做出反应的途径在动物中是保守的，类似的检查点可能在人类发育中也很重要。
Organisms in the wild develop with varying food availability. During periods of nutritional scarcity, development may slow or arrest until conditions improve. The ability to modulate developmental programs in response to poor nutritional conditions requires a means of sensing the changing nutritional environment and limiting tissue growth. The mechanisms by which organisms accomplish this adaptation are not well understood. We sought to study this question by examining the effects of nutrient deprivation on Caenorhabditis elegans development during the late larval stages, L3 and L4, a period of extensive tissue growth and morphogenesis. By removing animals from food at different times, we show here that specific checkpoints exist in the early L3 and early L4 stages that systemically arrest the development of diverse tissues and cellular processes. These checkpoints occur once in each larval stage after molting and prior to initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like growth factor receptor, regulates passage through the L3 and L4 checkpoints in response to nutrition. The FOXO transcription factor DAF-16, a major target of insulin-like signaling, functions cell-nonautonomously in the hypodermis (skin) to arrest developmental upon nutrient removal. The effects of DAF-16 on progression through the L3 and L4 stages are mediated by DAF-9, a cytochrome P450 ortholog involved in the production of C. elegans steroid hormones. Our results identify a novel mode of C. elegans growth in which development progresses from one checkpoint to the next. At each checkpoint, nutritional conditions determine whether animals remain arrested or continue development to the next checkpoint. Organisms in the wild often face long periods in which food is scarce. This may occur due to seasonal effects, loss of territory, or changes in predator-to-prey ratio. During periods of scarcity, organisms undergo adaptations to conserve resources and prolong survival. When nutrient deprivation occurs during development, physical growth and maturation to adulthood is delayed. These effects are also observed in malnourished individuals, who are smaller and reach puberty at later ages. Developmental arrest in response to nutrient scarcity requires a means of sensing changing nutrient conditions and coordinating an organism-wide response. How this occurs is not well understood. We assessed the developmental response to nutrient withdrawal in the nematode worm Caenorhabditis elegans. By removing food in the late larval stages, a period of extensive tissue formation, we have uncovered previously unknown checkpoints that occur at precise times in development. Diverse tissues and cellular processes arrest at the checkpoints. Insulin-like signaling and steroid hormone signaling regulate tissue arrest following nutrient withdrawal. These pathways are conserved in mammals and are linked to growth processes and diseases. Given that the pathways that respond to nutrition are conserved in animals, it is possible that similar checkpoints may also be important in human development.
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影响因子：
11.8
作者：
Gerisch, B;Weitzel, C;Antebi, A
通讯作者：
Antebi, A
影响因子：
56.9
作者：
Arantes-Oliveira, N;Apfeld, J;Kenyon, C
通讯作者：
Kenyon, C
影响因子：
48
作者：
Calixto, Andrea;Chelur, Dattananda;Topalidou, Irini;Chen, Xiaoyin;Chalfie, Martin
通讯作者：
Chalfie, Martin
影响因子：
9.8
作者：
Bridgham, Jamie T.;Eick, Geeta N.;Thornton, Joseph W.
通讯作者：
Thornton, Joseph W.
DOI：
10.1073/pnas.1106556108
发表时间：
2011-08-30
影响因子：
11.1
作者：
Callier, Viviane;Nijhout, H. Frederik
通讯作者：
Nijhout, H. Frederik