Transcriptional control of neuronal plasticity by daf-16/FoxO

许多神经元表现出非凡的能力来改变特定的表型特性 内部或外部环境的变化。这种“神经元可塑性”现象必须 与定义完全差异化状态的基因硬连接的监管计划相交 神经元。我们建议在这里研究这种硬连线的基因调控程序是如何被修改的 使神经系统能够在特定的条件下改变神经元的特定表型 条件。我们在线虫C.的背景下研究了单神经元分辨率问题。 其神经系统根据系统发育改变了许多特征的秀丽动物 保守的胰岛素/IGF1样激素信号系统。我们在这份赠款提案中提出并测试了 胰岛素/IGF-1调控的DAF-16/FoxO转录因子在许多细胞中自主作用 控制上调或下调的特定靶基因表达的不同神经元类型 以响应特定的环境条件。我们提出并测试了DAF-16/FoxO的协同工作 通过神经元型特异性末端选择器转录来促进或拮抗 这些转录因子控制它们的效应器基因。

Many neurons display the remarkable ability to alter specific phenotypic properties in response to changes in the internal or external environment. Such “neuronal plasticity” phenomena must intersect with genetically hardwired regulatory programs that define the fully differentiated state of a neuron. We propose here to investigate how such hardwired gene regulatory programs are modified to enable the nervous system to change specific phenotypic aspects of a neuron under specific conditions. We study this problem with single neuron resolution in the context of the nematode C. elegans whose nervous system remodels a number of features in response to the phylogenetically conserved insulin/IGF1-like hormonal signaling system. We propose and test in this grant proposal that the insulin/IGF-1-controlled DAF-16/FoxO transcription factors acts cell autonomously in many different neuron types to control the expression of specific target genes that are up- or downregulated in response to specific environmental conditions. We propose and test that DAF-16/FoxO cooperates with neuron-type specific terminal selector transcription to either promote or antagonize the ability of these transcription factors to control their effector genes.