Molecular profiling of gamma motor neuron development

伽马运动神经元发育的分子谱

基本信息

批准号：
8029367
负责人：
Neil Alan Shneider
金额：
$ 24.15万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8029367
关键词：
Accounting Animal Model Animals Apoptosis Behavior Behavior Disorders Candidate Disease Gene Cellular biology Dependence Development Disease Embryo Embryonic Development Fiber Future GDNF gene GDNF receptors Gamma Motor Neurons Gene Expression Genes Genetic Genetic Markers Health In Situ Hybridization In Vitro Limb structure Mechanoreceptors Modeling Molecular Molecular Analysis Molecular Genetics Molecular Profiling Motor Motor Neurons Mus Muscle Muscle Spindles Mutant Strains Mice Neuraxis Neurons Pattern Perception Phenotype Physiological Play Property Reporting Role Sampling Series Signal Transduction Skeletal Muscle Specific qualifier value Spinal Spinal Cord Staging Stretch Receptors Stretching System Tissue-Specific Gene Expression Transgenes Validation Wild Type Mouse Work base embryonic stem cell in vivo laser capture microdissection molecular size motor control motor neuron development mutant nerve supply novel postnatal programs public health relevance research study selective expression sensory feedback

Accounting Animal Model Animals Apoptosis Behavior Behavior Disorders Candidate Disease Gene Cellular biology Dependence Development Disease Embryo Embryonic Development Fiber Future GDNF gene GDNF receptors Gamma Motor Neurons Gene Expression Genes Genetic Genetic Markers Health In Situ Hybridization In Vitro Limb structure Mechanoreceptors Modeling Molecular Molecular Analysis Molecular Genetics Molecular Profiling Motor Motor Neurons Mus Muscle Muscle Spindles Mutant Strains Mice Neuraxis Neurons Pattern Perception Phenotype Physiological Play Property Reporting Role Sampling Series Signal Transduction Skeletal Muscle Specific qualifier value Spinal Spinal Cord Staging Stretch Receptors Stretching System Tissue-Specific Gene Expression Transgenes Validation Wild Type Mouse Work base embryonic stem cell in vivo laser capture microdissection molecular size motor control motor neuron development mutant nerve supply novel postnatal programs public health relevance research study selective expression sensory feedback

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项目摘要

DESCRIPTION (provided by applicant): Gamma motor neurons (g-MNs) are a functionally and anatomically distinct subclass of neurons found in large number in most motor pools. These "fusimotor" neurons exclusively innervate the intrafusal fibers of the muscle spindle and comprise a parallel motor system that activates muscle spindle fibers independently of extrafusal muscle. The mechanisms that control the specification and differentiation of g-MNs are unknown, and no specific markers have been identified to distinguish g from a motor neurons in early development. We have found that g fusimotor neurons are selectively dependent on target muscle spindle-derived GDNF, and a recent study reports that fusimotor neurons are also selectively dependent on GDNF signaling in embryogenesis. Using this trophic requirement as a functional marker, we propose to perform a differential screen for genes selectively expressed in g-MNs using a mutant mouse in which g- MN precursors are selectively lost in the absence of GDNF signaling. We will also exploit this specific property of g-MNs in cultures of mouse embryonic stem cell-derived motor neurons to profile the pattern of gene expression in g-MNs in vitro. Finally, we will use molecular and size criteria established in our previous work to selectively isolate postnatal g-MNs for molecular analysis. The identification of genes specifically expressed in g-MNs at different stages of development will make possible a molecular genetic approach to study the formation and function of the fusimotor system, including its role in normal motor behaviors and disorders of motor control. PUBLIC HEALTH RELEVANCE: Gamma motor neurons regulate sensory feedback to the central nervous system from the periphery by controlling the sensitivity of stretch receptors in skeletal muscle. Their function is critical for motor control and for our perception of where our limbs are in space. This study will provide a molecular profile of gamma motor neurons, opening the way to future study of this motor system in health and disease.

描述（由申请人提供）：伽马运动神经元（G-MNS）是大多数运动池中大数量中发现的神经元的功能和解剖上不同的子类。这些“融合型”神经元仅支配着肌肉纺锤体的恒星内纤维，并组成平行运动系统，该系统独立于肌肉外肌肉而激活肌肉纺锤体纤维。控制G-MN的规范和分化的机制尚不清楚，并且尚未确定特定的标记以将G与运动神经元与早期发育中的运动神经元区分开。我们已经发现，G融合神经元有选择地依赖于靶肌纺锤体衍生的GDNF，最近的一项研究报告说，融合神经元也有选择地依赖于胚胎发生中的GDNF信号。使用此营养需求作为功能标记，我们建议使用突变小鼠在G-MN中选择性地表达差异屏幕，其中G-MN前体在没有GDNF信号传导的情况下选择性地丢失了G-MN前体。我们还将利用G-MN在小鼠胚胎干细胞衍生的运动神经元培养物中的这种特定特性，以介绍G-MNS体外G-MN中基因表达的模式。最后，我们将使用先前工作中建立的分子和大小标准来选择性地分离出产后G-MN进行分子分析。在不同发育阶段在G-MN中特异性表达的基因的鉴定将使可能成为研究融合系统形成和功能的分子遗传方法，包括其在正常运动行为和运动控制的疾病中的作用。公共卫生相关性：伽马运动神经元通过控制骨骼肌中拉伸受体的敏感性来调节中枢神经系统的感觉反馈。它们的功能对于运动控制和我们对四肢在太空中的位置至关重要。这项研究将提供伽马运动神经元的分子特征，为这种运动系统在健康和疾病中的未来研究开辟道路。