DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling.
DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling.
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DOI：
10.1371/journal.pbio.3001204
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发表时间：
2021-04
期刊：
影响因子：
9.8
通讯作者：
Hobert O
中科院分区：
文献类型：
--
作者：
Aghayeva U;Bhattacharya A;Sural S;Jaeger E;Churgin M;Fang-Yen C;Hobert O
许多细胞类型显示出响应特定的外部或内部信号而改变其细胞表型的显著能力。当不利的环境条件触发进入dauer滞育阶段时，这种表型可塑性在秀丽隐杆线虫中是明显的。这种进入伴随着动物的许多不同组织类型的结构、分子和功能重塑，包括其神经系统。3种不同激素信号传导系统的转录因子（TF）效应物，胰岛素应答性β 1 -16/FoxO TF、TGFβ应答性β 2 -3/SMAD TF和类固醇核激素受体β 1 -12/VDR（维生素D受体（VDR）的同源物），先前已证明是进入Dauer停滞期所需的，但是它们对潜在的细胞重塑过程的细胞和时间作用焦点仍然不完全清楚。通过产生条件等位基因，使我们能够在空间和时间上控制基因活性，我们在这里表明，所有3个TF不仅需要启动组织重塑进入dauer阶段后，如前所示，但也不断需要保持重塑状态。我们发现，在感觉神经元中需要ESTA-3/SMAD来促进并维持动物范围内的组织重塑事件。相比之下，β-16/FoxO或β-12/VDR细胞自主地控制特定细胞类型中的解剖、分子和行为重塑事件。有趣的是，我们还发现了在神经系统重塑中，β-16/FoxO和β-12/VDR的非细胞自主功能，表明存在几个胰岛素依赖的器官间信号传导轴。我们的发现为激素系统如何控制组织重塑提供了新的视角。这项研究探讨了线虫线虫滞育期间细胞可塑性的机制，揭示了这是通过不同的生物控制的转录因子组合的器官间信号传导控制的; FoxO同源物16和维生素D受体同源物12。
Many cell types display the remarkable ability to alter their cellular phenotype in response to specific external or internal signals. Such phenotypic plasticity is apparent in the nematode Caenorhabditis elegans when adverse environmental conditions trigger entry into the dauer diapause stage. This entry is accompanied by structural, molecular, and functional remodeling of a number of distinct tissue types of the animal, including its nervous system. The transcription factor (TF) effectors of 3 different hormonal signaling systems, the insulin-responsive DAF-16/FoxO TF, the TGFβ-responsive DAF-3/SMAD TF, and the steroid nuclear hormone receptor, DAF-12/VDR, a homolog of the vitamin D receptor (VDR), were previously shown to be required for entering the dauer arrest stage, but their cellular and temporal focus of action for the underlying cellular remodeling processes remained incompletely understood. Through the generation of conditional alleles that allowed us to spatially and temporally control gene activity, we show here that all 3 TFs are not only required to initiate tissue remodeling upon entry into the dauer stage, as shown before, but are also continuously required to maintain the remodeled state. We show that DAF-3/SMAD is required in sensory neurons to promote and then maintain animal-wide tissue remodeling events. In contrast, DAF-16/FoxO or DAF-12/VDR act cell-autonomously to control anatomical, molecular, and behavioral remodeling events in specific cell types. Intriguingly, we also uncover non-cell autonomous function of DAF-16/FoxO and DAF-12/VDR in nervous system remodeling, indicating the presence of several insulin-dependent interorgan signaling axes. Our findings provide novel perspectives into how hormonal systems control tissue remodeling. This study explores the mechanisms governing cellular plasticity during diapause in the nematode Caenorhabditis elegans, revealing that this is controlled by inter-organ signaling via a combination of different hormone-controlled transcription factors; the FoxO homolog DAF-16 and the vitamin D receptor homolog DAF-12.
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影响因子：
4.1
作者：
Cui, Xiaoying;Gooch, Helen;Eyles, Darryl
通讯作者：
Eyles, Darryl
DOI：
10.1007/978-1-4939-2842-2_14
发表时间：
2015-01-01
期刊：
C. ELEGANS: METHODS AND APPLICATIONS, 2ND EDITION
影响因子：
--
作者：
Churgin, Matthew A.;Fang-Yen, Christopher
通讯作者：
Fang-Yen, Christopher
DOI：
10.1186/2046-2395-3-5
发表时间：
2014
期刊：
Longevity & healthspan
影响因子：
--
作者：
Bansal A;Kwon ES;Conte D Jr;Liu H;Gilchrist MJ;MacNeil LT;Tissenbaum HA
通讯作者：
Tissenbaum HA
影响因子：
4.6
作者：
Etchberger, John F.;Flowers, Eileen B.;Hobert, Oliver
通讯作者：
Hobert, Oliver
影响因子：
2.7
作者：
CASSADA, RC;RUSSELL, RL
通讯作者：
RUSSELL, RL