Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.
Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.
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DOI：
10.1371/journal.pgen.1003133
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Lee SJ
中科院分区：
文献类型：
--
作者：
Gaglia MM;Jeong DE;Ryu EA;Lee D;Kenyon C;Lee SJ
多细胞生物的感觉系统旨在提供有关环境的信息，从而引起生理和行为的适当变化。在秀丽隐杆线虫中，感觉神经元影响发育过程中滞育状态下的决定，并调节成年动物的寿命。然而，这些效应背后的机制尚不完全清楚。利用全基因组微阵列分析，我们鉴定出了受鞭毛内转运蛋白daf-10突变影响的转录本水平，这导致秀丽隐杆线虫许多感觉神经元的发育和功能受损。与已有的遗传学数据一致，转录因子DAF-16/FOXO调控基因的表达受到daf-10突变的影响。此外，我们发现daf-10突变体中DAF-12/核激素受体转录靶点的表达改变，并表明该途径特异性影响这些动物的水形成表型。出乎意料的是，病原体反应基因在daf-10突变动物中被抑制，这些感觉突变体对细菌病原体表现出改变的易感性和行为回避。此外，我们发现由daf-10突变诱导的溶质转运基因mct-1/2对长寿是必要和充分的。因此，感觉输入似乎影响了一个广泛的转录网络，调节秀丽隐杆线虫的基本生物过程。这种情况让人想起哺乳动物下丘脑对生理的复杂调节，下丘脑也接受来自感觉系统的神经支配，尤其是视觉和嗅觉系统。感官为动物提供有关环境的信息，这些信息不仅影响它们的行为，还影响它们的内部状态和生理输出。这些信息是如何处理的尚不清楚。在这项研究中，我们使用具有缺陷的感觉神经元的突变秀丽隐杆线虫来研究感觉变化如何改变基因表达和调节生理，特别是蠕虫在生长过程中冬眠的选择和它们作为成年虫的寿命。我们发现，感觉神经元的缺陷改变了基因表达的模式，并通过已知的激素途径（包括胰岛素/IGF-1和类固醇途径）调节这些输出。我们还发现了一种新的长寿调节因子，MCT-1，预计它会在体内运输小代谢物和激素。出乎意料的是，我们发现感觉障碍改变了另一种生理输出，即对传染性病原体的反应。它阻止了蠕虫避开感染性细菌，减少了潜在保护因子的表达，但也增加了蠕虫对感染的抵抗力，这表明对环境刺激的反应是一个复杂的网络。了解感觉信息是如何在这种相对简单的生物中传递的，可能会让我们了解哺乳动物等高等生物的感觉处理过程。
The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems. The senses provide animals with information about their environment, which affects not only their behavior but also their internal state and physiological outputs. How this information is processed is still unclear. In this study, we used mutant C. elegans roundworms that had defective sensory neurons to investigate how changes in sensation alter the expression of genes and regulate physiology, specifically the worms' choice to hibernate during growth and their longevity as fully-grown adults. We showed that defects in sensory neurons change the pattern of gene expression and regulate these outputs through known hormonal pathways, including insulin/IGF-1 and steroid pathways. We also identified a new regulator of longevity, MCT-1, that is predicted to transport small metabolites and hormones in the body. Unexpectedly, we found that sensory impairment altered yet another physiological output, the response to infectious agents. It prevented the worms from avoiding infectious bacteria and reduced the expression of potentially protective factors, but also increased the worms' resistance to infection, suggesting a complex network of responses to environmental stimuli. Understanding how sensory information is relayed in this relatively simple organism may inform our understanding of sensory processing in higher organisms like mammals.
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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：
7.8
作者：
Fisher, AL;Lithgow, GJ
通讯作者：
Lithgow, GJ
影响因子：
56.9
作者：
Garsin, DA;Villanueva, JM;Ausubel, FM
通讯作者：
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影响因子：
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作者：
Baldi, P;Long, AD
通讯作者：
Long, AD
DOI：
10.1073/pnas.0914643107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Estes, Kathleen A.;Dunbar, Tiffany L.;Troemel, Emily R.
通讯作者：
Troemel, Emily R.