Molecular profiling of gamma motor neuron development

伽马运动神经元发育的分子谱

• 批准号: 8130880
• 负责人: Neil Alan Shneider
• 金额: $ 19.72万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8130880
• 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; Messenger RNA; 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

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-MN）是在大多数运动池中大量发现的功能和解剖学上不同的神经元亚类。这些“梭运动”神经元专门支配肌梭的梭内纤维，并且包括独立于梭外肌激活肌梭纤维的平行运动系统。控制g-MNs的规范和分化的机制是未知的，并没有特定的标记物已被确定，以区分在早期发展的g运动神经元。我们已经发现，g fusimotor神经元选择性依赖于靶肌梭源性GDNF，最近的一项研究报告，fusimotor神经元也选择性依赖于GDNF信号在胚胎发育。使用这种营养需求作为功能标记，我们建议使用突变小鼠对g-MN中选择性表达的基因进行差异筛选，其中g-MN前体在GDNF信号传导的情况下选择性丢失。我们还将利用这一特定的属性，在小鼠胚胎干细胞衍生的运动神经元的培养物中的g-MN的基因表达的模式在体外。最后，我们将使用我们以前的工作中建立的分子和大小标准来选择性地分离出生后的g-MN进行分子分析。在不同发育阶段的g-MN中特异性表达的基因的鉴定将使研究梭动系统的形成和功能，包括其在正常运动行为和运动控制障碍中的作用的分子遗传学方法成为可能。 公共卫生相关性：γ运动神经元通过控制骨骼肌中牵张感受器的敏感性来调节从外周到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感知四肢在空间中的位置至关重要。这项研究将提供伽马运动神经元的分子概况，为未来研究健康和疾病中的运动系统开辟道路。

项目成果

Wnt7A identifies embryonic γ-motor neurons and reveals early postnatal dependence of γ-motor neurons on a muscle spindle-derived signal.

• DOI: 10.1523/jneurosci.1160-12.2012
• 发表时间: 2012-06-20
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Ashrafi S;Lalancette-Hébert M;Friese A;Sigrist M;Arber S;Shneider NA;Kaltschmidt JA
• 通讯作者: Kaltschmidt JA