A Caenorhabditis elegans developmental decision requires insulin signaling-mediated neuron-intestine communication.
A Caenorhabditis elegans developmental decision requires insulin signaling-mediated neuron-intestine communication.
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DOI：
10.1242/dev.103846
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Zhen M
中科院分区：
文献类型：
--
作者：
Hung WL;Wang Y;Chitturi J;Zhen M
不利的环境条件触发C。elegans幼虫激活另一种发育程序，称为dauer滞育，这使他们能够抵抗压力。高水平胰岛素信号传导阻止组成性dauer形成。然而，动物如何评估条件以选择最佳发育程序还不完全清楚。在这里，我们表明，胰岛素样肽（ILP）介导的神经元肠通信发挥了作用，在这一发展的决定。与以前的研究结果一致，并扩展，我们表明，INS-4，INS-6和INS-28的同时去除导致完全渗透的本构染料的形成，而INS-1和INS-18的去除显着抑制本构染料的形成。这些配体由前蛋白转化酶PC 1/KPC-1和/或PC 2/EGL-3加工。激动性和拮抗性配体由神经元表达并在神经元中起作用以防止或促进dauer形成。相比之下，胰岛素受体β 2及其效应子FOXO转录因子β 16仅在肠道中发挥作用，以调节进入滞育的决定。这些结果表明，神经系统通常建立了一个激动性ILP占主导地位的范例，以抑制肠道β-16活化，并允许生殖发育。在不利的条件下，激动-拮抗ILP平衡的转换激活肠道β-16，使动物进入滞育。
Adverse environmental conditions trigger C. elegans larvae to activate an alternative developmental program, termed dauer diapause, which renders them stress resistant. High-level insulin signaling prevents constitutive dauer formation. However, it is not fully understood how animals assess conditions to choose the optimal developmental program. Here, we show that insulin-like peptide (ILP)-mediated neuron-intestine communication plays a role in this developmental decision. Consistent with, and extending, previous findings, we show that the simultaneous removal of INS-4, INS-6 and DAF-28 leads to fully penetrant constitutive dauer formation, whereas the removal of INS-1 and INS-18 significantly inhibits constitutive dauer formation. These ligands are processed by the proprotein convertases PC1/KPC-1 and/or PC2/EGL-3. The agonistic and antagonistic ligands are expressed by, and function in, neurons to prevent or promote dauer formation. By contrast, the insulin receptor DAF-2 and its effector, the FOXO transcription factor DAF-16, function solely in the intestine to regulate the decision to enter diapause. These results suggest that the nervous system normally establishes an agonistic ILP-dominant paradigm to inhibit intestinal DAF-16 activation and allow reproductive development. Under adverse conditions, a switch in the agonistic-antagonistic ILP balance activates intestinal DAF-16, which commits animals to diapause.
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影响因子：
48
作者：
Frokjaer-Jensen, Christian;Davis, M. Wayne;Hollopeter, Gunther;Taylor, Jon;Harris, Todd W.;Nix, Paola;Lofgren, Rachel;Prestgard-Duke, Michael;Bastiani, Michael;Moerman, Donald G.;Jorgensen, Erik M.
通讯作者：
Jorgensen, Erik M.
影响因子：
11.8
作者：
Gerisch, B;Weitzel, C;Antebi, A
通讯作者：
Antebi, A
DOI：
10.1159/000468903
发表时间：
1991-01-01
期刊：
ENZYME
影响因子：
--
作者：
BAILYES, EM;BENNETT, DL;HUTTON, JC
通讯作者：
HUTTON, JC
影响因子：
4.3
作者：
Kaletsky, Rachel;Murphy, Coleen T.
通讯作者：
Murphy, Coleen T.
影响因子：
2.7
作者：
CASSADA, RC;RUSSELL, RL
通讯作者：
RUSSELL, RL