Repression of an activity-dependent autocrine insulin signal is required for sensory neuron development in C. elegans
Repression of an activity-dependent autocrine insulin signal is required for sensory neuron development in C. elegans
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DOI：
10.1242/dev.182873
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发表时间：
2019-11-15
期刊：
影响因子：
4.6
通讯作者：
Ringstad, Niels
中科院分区：
文献类型：
--
作者：
Horowitz, Lauren Bayer;Brandt, Julia P.;Ringstad, Niels
神经系统的发育是由遗传程序指导的，并通过将神经活动与基因表达相结合的不同机制进行优化。人们对这些过程是如何整合的仍知之甚少。在这里，我们报告了在秀丽线虫神经系统发育过程中胰岛素样肽(ILPS)的调节释放实现了这种整合。我们发现，p38 MAP激酶PMK-3是化学感觉BAG神经元分化所必需的，它限制了ILP信号，抑制了BAG神经元命运的表达。ILPS在发育过程中以一种活性依赖的方式从BAG自身释放，表明ILPS构成了调节BAG神经元分化的自分泌信号。因此，特定神经元命运的表达受到遗传程序和神经活动的协调调节，遗传程序设定发育过程中ILP的表达水平，神经活动调节ILP的释放。这种自分泌信号可能具有一般性和保守性的功能，在神经发育过程中具有具有活动依赖机制的确定性遗传程序的整合功能。
Nervous system development is instructed by genetic programs and refined by distinct mechanisms that couple neural activity to gene expression. How these processes are integrated remains poorly understood. Here, we report that the regulated release of insulin-like peptides (ILPs) during development of the Caenorhabditis elegans nervous system accomplishes such an integration. We find that the p38 MAP kinase PMK-3, which is required for the differentiation of chemosensory BAG neurons, limits an ILP signal that represses expression of a BAG neuron fate. ILPs are released from BAGs themselves in an activity-dependent manner during development, indicating that ILPs constitute an autocrine signal that regulates the differentiation of BAG neurons. Expression of a specialized neuronal fate is, therefore, coordinately regulated by a genetic program that sets levels of ILP expression during development, and by neural activity, which regulates ILP release. Autocrine signals of this kind might have general and conserved functions as integrators of deterministic genetic programs with activity-dependent mechanisms during neurodevelopment.