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The Genetic Basis of Hypocretin Neuronal Specification.

下丘脑分泌素神经元规格的遗传基础。

基本信息

批准号：
8706249
负责人：
Justin Liu
金额：
$ 1.1万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2014-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8706249
关键词：
Antisense Oligonucleotides Behavior Biological Models Candidate Disease Gene Cells Cloning Cues Development Developmental Process Embryo Excessive Daytime Sleepiness Fertilization Fishes Flow Cytometry Fluorescent in Situ Hybridization Gene Expression Gene Expression Profiling Generations Genes Genetic Heat-Shock Response Hour Human Hypothalamic structure In Situ Hybridization In Vitro Larva Lateral Lead Mammals Measures Microarray Analysis Modeling Monitor Narcolepsy Nervous system structure Neurons Neuropeptides Partner in relationship Patients Performance Phenotype Play Population Proteins Research Role Signal Transduction Sleep Sleep Disorders Specific qualifier value System Techniques Testing Time To specify Transgenic Organisms Wakefulness Zebrafish base cost enhanced green fluorescent protein hypocretin improved in vivo knock-down nervous system disorder neuron development novel null mutation overexpression prevent promoter protein expression red fluorescent protein relating to nervous system research study transcription factor zinc finger nuclease

项目摘要

DESCRIPTION (provided by applicant): Sleep is an evolutionarily conserved behavior that is important for neural performance and function, yet the genes and neurons that regulate sleep are poorly understood. The best-characterized sleep regulators are the hypocretin neuropeptides, which promote wakefulness and inhibit sleep. Loss of hypocretin neurons causes narcolepsy, an incurable neurological disorder characterized by excessive daytime sleepiness and fragmented sleep/wake states. Hypocretin neurons thus play a critical role in regulating sleep, but virtually nothing is known about factors that regulate their specification. Preliminary studies in the zebrafish, Danio rerio, have identified 19 genes with enriched expression in hypocretin neurons. I will test the hypothesis that some of these genes are necessary and/or sufficient to specify the hypocretin neuronal fate. Identifying such factors will greatly expand our understanding of hypocretin neuronal development, and may elucidate how these neurons are assembled into a functional sleep circuit. Ultimately, these experiments could lead to novel therapies that prevent or reverse the loss of hypocretin neurons in patients with narcolepsy.

描述(申请人提供)：睡眠是一种进化保守的行为，对神经表现和功能很重要，但调节睡眠的基因和神经元却知之甚少。最具特点的睡眠调节剂是下丘脑素神经肽，它促进觉醒并抑制睡眠。下丘脑分泌素神经元的缺失会导致发作性睡病，这是一种无法治愈的神经疾病，其特征是白天过度嗜睡和睡眠/醒来状态支离破碎。因此，下丘脑岛神经元在调节睡眠方面起着关键作用，但对调节其特性的因素几乎一无所知。对斑马鱼Danio rerio的初步研究发现，有19个基因在下丘脑神经元中有丰富表达。我将测试这样的假设，即这些基因中的一些是必要的和/或足以确定下丘脑克汀神经元的命运。识别这些因素将极大地扩展我们对下丘脑神经发育的理解，并可能阐明这些神经元是如何组装成一个功能性睡眠回路的。最终，这些实验可能会导致新的疗法，防止或逆转发作性睡病患者下丘脑神经元体的丢失。