Transcriptional control of neuronal plasticity by daf-16/FoxO

daf-16/FoxO 对神经元可塑性的转录控制

• 批准号: 9914697
• 负责人: Oliver Hobert
• 金额: $ 44.55万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9914697
• 关键词: Animals; Applications Grants; Biochemical; Caenorhabditis elegans; Cell Nucleus; Cells; Communication; Cues; Electrical Synapse; Endocrine system; Environment; Event; G-Protein-Coupled Receptors; Gene Expression; Genes; Genetic; Genetic Transcription; Goals; IGF1 gene; Individual; Insulin; Insulin-Like Growth Factor I; Insulin-Like Growth Factor Receptor; Invertebrates; Life; Nematoda; Nervous system structure; Neuronal Plasticity; Neurons; Neuropeptide Gene; Neuropeptides; Nuclear Translocation; Pathway interactions; Perception; Phenotype; Phylogenetic Analysis; Property; Regulator Genes; Repression; Resolution; Sensory; Signal Transduction; Specificity; Stimulus; System; Technology; Testing; Transcriptional Regulation; cell type; gene repression; genetic analysis; hormonal signals; mutant; programs; response; transcription factor

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.

许多神经元表现出改变特定表型特性以响应的显着能力 这种“神经元可塑性”现象必定是内部或外部环境的变化。 与定义完全分化状态的基因硬连线监管程序相交叉 我们在这里建议研究如何修改这种硬连线基因调控程序。 使神经系统能够在特定的条件下改变神经元的特定表型方面 我们在线虫 C 的背景下用单神经元分辨率研究这个问题。 线虫的神经系统根据系统发育重塑了许多特征 我们在此拨款提案中提出并测试了保守的胰岛素/IGF1 样激素信号系统。 胰岛素/IGF-1控制的DAF-16/FoxO转录因子在许多细胞中自主作用于细胞 不同的神经元类型来控制上调或下调的特定靶基因的表达 针对特定的环境条件，我们提出并测试了DAF-16/FoxO的配合。 具有神经元类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基因。

项目成果

DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling.

• DOI: 10.1371/journal.pbio.3001204
• 发表时间: 2021-04
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Aghayeva U;Bhattacharya A;Sural S;Jaeger E;Churgin M;Fang-Yen C;Hobert O
• 通讯作者: Hobert O

A panel of fluorophore-tagged daf-16 alleles.

• DOI: 10.17912/micropub.biology.000210
• 发表时间: 2020-01-07
• 期刊: microPublication biology
• 作者: Aghayeva, Ulkar;Bhattacharya, Abhishek;Hobert, Oliver
• 通讯作者: Hobert, Oliver