Feeding state, insulin and NPR-1 modulate chemoreceptor gene expression via integration of sensory and circuit inputs.
Feeding state, insulin and NPR-1 modulate chemoreceptor gene expression via integration of sensory and circuit inputs.
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DOI：
10.1371/journal.pgen.1004707
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发表时间：
2014-10
期刊：
影响因子：
4.5
通讯作者：
van der Linden AM
中科院分区：
文献类型：
--
作者：
Gruner M;Nelson D;Winbush A;Hintz R;Ryu L;Chung SH;Kim K;Gabel CV;van der Linden AM
进食状态和食物可获得性可以显著改变动物对环境中化学物质的感觉反应。化学感受器基因表达的动态变化可能是化学感受行为中某些食物和状态依赖性变化的基础，但这些表达变化的机制尚不清楚。在此，我们在C.其在ADL感觉神经元类型中的表达受感觉和内部进食状态信号的整合调节。我们发现，除了KIN-29，信号传导是由β 2胰岛素样受体，OCR-2 TRPV通道，和NPR-1神经肽受体介导的。细胞特异性拯救实验表明，NPR-2和OCR-2在ADL中起作用，而NPR-1在RMG中间神经元中起作用。NPR-1介导的调节srh-234依赖于缝隙连接，这意味着电路输入调节感觉神经元中化学感受器基因的表达。使用物理和遗传操纵的ADL神经元，我们表明，从食物的存在和ADL神经输出的感觉输入调节srh-234的表达。KIN-29和NPR-2主要通过MEF-2（MEF 2）和NPR-16（FOXO）转录因子调节ADL神经元中的srh-234表达，而OCR-2和NPR-1可能通过钙依赖性但不依赖于MEF-2和NPR-16的途径起作用。总之，我们的研究结果表明，感觉和电路介导的调控化学感受器基因通过多种途径，可以让动物精确地调节和微调其化学感受器的反应作为内部和外部条件的功能。当饥饿时，动物会戏剧性地改变它们对有吸引力和有害的化学刺激的化学感受行为。这可以使它们改变和优化它们的食物搜索策略，以增加它们的生存和繁殖。在鱼类、昆虫和线虫中观察到专门检测环境刺激的化学感受器的基因表达的变化，并且可能是在饥饿动物中观察到的化学感受行为变化的一般机制。为了阐明这一机制，我们已经开发了一种体内报告基因检测方法。elegans用于监测候选化学感受器基因在单一感觉神经元类型（称为ADL）中的表达，作为进食状态的函数。使用这种报告分析，我们表明，感觉输入到ADL和ADL的神经输出，以及从RMG interneuron，这是电连接到ADL的输入，需要微调化学受体基因在ADL中的表达。化学感受器基因表达的感觉和回路介导的调节依赖于多种途径，包括神经肽受体、NPR-1和胰岛素样受体α 2。我们的研究结果揭示了化学感受器基因表达的机制，并提供了深入了解化学感受器基因的表达变化可能有助于改变化学感觉行为作为一个功能的喂养状态。
Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions. Animals dramatically modify their chemosensory behaviors to attractive and noxious chemical stimuli when starved. This could allow them to alter and optimize their food-search strategies to increase their survival and reproduction. Changes in the gene expression of chemoreceptors specialized in detecting environmental stimuli is observed in fish, insects and nematodes, and may be a general mechanism underlying the changes in chemosensory behaviors observed in starved animals. To elucidate this mechanism, we have developed an in vivo reporter assay in C. elegans for monitoring the expression of a candidate chemoreceptor gene in a single sensory neuron type, called ADL, as a function of feeding state. Using this reporter assay, we show that sensory inputs into ADL and neural outputs from ADL, as well as inputs from the RMG interneuron, which is electrically connected to ADL, are required to fine-tune expression of chemoreceptor genes in ADL. Sensory and circuit-mediated regulation of chemoreceptor gene expression is dependent on multiple pathways, including the neuropeptide receptor, NPR-1, and the DAF-2 insulin-like receptor. Our results reveal mechanisms underlying chemoreceptor gene expression, and provide insight into how expression changes in chemoreceptor genes may contribute to changes in chemosensory behavior as a function of feeding state.
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DOI：
10.1242/dev.103846
发表时间：
2014-04
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Hung WL;Wang Y;Chitturi J;Zhen M
通讯作者：
Zhen M
影响因子：
9.6
作者：
Chaisson KE;Hallem EA
通讯作者：
Hallem EA
影响因子：
11.4
作者：
Ezcurra, Marina;Tanizawa, Yoshinori;Schafer, William R.
通讯作者：
Schafer, William R.
影响因子：
25
作者：
Chalasani, Sreekanth H.;Kato, Saul;Albrecht, Dirk R.;Nakagawa, Takao;Abbott, L. F.;Bargmann, Cornelia I.
通讯作者：
Bargmann, Cornelia I.
影响因子：
2.6
作者：
Forbes, WM;Ashton, FT;Schad, GA
通讯作者：
Schad, GA