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Regulation of Sensory-Motor Connectivity by Semaphorin-Plexin Signaling

信号蛋白-丛蛋白信号传导对感觉运动连接的调节

基本信息

批准号：
8442876
负责人：
Yutaka Yoshida
金额：
$ 31.03万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8442876
关键词：
Address Afferent Neurons Alkaline Phosphatase Amyotrophic Lateral Sclerosis Area Axon Behavior Behavioral Binding Biological Models Brain Brain Stem Breathing Cells Cholera Toxin Protomer B Cytoplasmic Tail Data Defect Deglutition Development Diagnosis Disease Embryo Family Fiber Genetic Goals Health Human In Situ Hybridization In Vitro Label Ligands Limb structure Methods Molecular Motor Motor Neuron Disease Motor Neurons Mus Muscle Mutant Strains Mice Nerve Neuraxis Neurons Peripheral Positioning Attribute Prevention therapy Proprioceptor Regulation Relative (related person)Role Semaphorins Sensory Signal Transduction Specificity Spinal Cord Spinal Ganglia Spinal Muscular Atrophy Spinal cord injury Staging Synapses Testing Tracer Ventral Roots Walking Work axon growth axon guidance base gain of function gray matter knowledge base mutant nervous system disorder neural circuit neuronal cell body plexin presynaptic receptor rectus femoris research study spinal reflex synaptogenesis therapy development vesicular glutamate transporter 1

项目摘要

DESCRIPTION (provided by applicant): Neurons make synaptic connections with a precise specificity in order to assemble neural circuits. Although molecules that control initial axonal trajectories are relatively well understood, it is largely unknown how precise synaptic connections are formed within the target area. The goal of this proposal is to understand the molecular basis of synapse formation and synaptic specificity in the developing mouse spinal cord. The spinal reflex circuit in the spinal cord is an excellent model system to study synapse formation and synaptic specificity because of its relative simplicity and availability of abundant knowledge based on previous anatomical and electrophysiological studies. Cell bodies in the ventral gray matter are grouped into "motor neuron pools", which project axons to specific muscles. There are approximately fifty such motor neuron pools at the levels of the limbs in the mouse spinal cord. "Proprioceptive sensory neurons", which innervate these muscles with proprioceptive fibers, have their cell bodies in the dorsal root ganglia (DRG), and project axons into the spinal cord, which terminate and make synapses with the appropriate motor neuron pools. Our preliminary data strongly suggest that the semaphorin (sema) family of signaling ligands, and their receptors, the plexins, control synapse formation and synaptic specificity of the sensory-motor connections. First, of all semas and plexins, expression of only plexinA1, plexinD1, and sema6B is highly enriched in proprioceptive sensory neurons. Second, sema6D and its receptor plexinA1 are expressed by motor and proprioceptive sensory neurons when synaptogenesis is occurring. Third, plexinD1 is expressed by subsets of proprioceptive sensory neurons, while its ligand sema3E is expressed by subsets of motor neurons. We hypothesize that sema-plexin combinations contro l synapse formation and synaptic specificity in the developing spinal cord. The first aim will examine whether sema6D-plexinA1 signaling regulates synapse formation of sensory-motor connections. The second and third aims will examine if sema3E- plexinD1 and plexinA4-sema6B signaling control synaptic specificity of sensory-motor connections. We will address these issues by using a combination of anatomical, electrophysiological, behavioral, and in vitro analyses together with mouse genetics.

描述（由申请人提供）：神经元以精确的特异性进行突触连接，以组装神经回路。虽然控制轴突初始轨迹的分子相对较好地理解，但在靶区域内如何形成精确的突触连接在很大程度上是未知的。这个计划的目的是了解发育中的小鼠脊髓中突触形成和突触特异性的分子基础。脊髓反射回路是研究突触形成和突触特异性的一个很好的模型系统，因为它相对简单，并且基于先前的解剖学和电生理学研究的丰富知识。腹侧灰质中的细胞体组成“运动神经元池”，将轴突投射到特定的肌肉。在小鼠脊髓的四肢水平上，大约有50个这样的运动神经元池。用本体感受纤维支配这些肌肉的“本体感受感觉神经元”在背根神经节（DRG）中具有它们的细胞体，并且将轴突投射到脊髓中，其终止并与适当的运动神经元池形成突触。我们的初步数据强烈表明，信号配体的semaphorin（sema）家族，及其受体，丛蛋白，控制突触的形成和突触特异性的感觉-运动连接。首先，在所有sema和丛蛋白中，仅丛蛋白A1、丛蛋白D1和sema 6 B的表达在本体感觉神经元中高度富集。第二，当突触发生时，运动和本体感觉神经元表达sema 6D及其受体plexinA 1。第三，plexinD 1由本体感觉神经元的亚群表达，而其配体sema 3E由运动神经元的亚群表达。我们假设sema-plexin组合控制发育中脊髓的突触形成和突触特异性。第一个目标将检查是否sema 6D-plexinA 1信号调节突触形成的感觉运动连接。第二和第三个目标将检查sema 3E-plexinD 1和plexinA 4-sema 6 B信号传导是否控制感觉-运动连接的突触特异性。我们将通过结合解剖学、电生理学、行为学和体外分析以及小鼠遗传学来解决这些问题。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Semaphorin signaling in vertebrate neural circuit assembly.

DOI：
10.3389/fnmol.2012.00071
发表时间：
2012
期刊：
Frontiers in molecular neuroscience
影响因子：
4.8
作者：
Yoshida Y
通讯作者：
Yoshida Y

Roles of semaphorin-6B and plexin-A2 in lamina-restricted projection of hippocampal mossy fibers.

DOI：
10.1523/jneurosci.0073-10.2010
发表时间：
2010-05-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Tawarayama H;Yoshida Y;Suto F;Mitchell KJ;Fujisawa H
通讯作者：
Fujisawa H

Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition.

DOI：
10.1038/nature08000
发表时间：
2009-06-11
期刊：
NATURE
影响因子：
64.8
作者：
Pecho-Vrieseling, Eline;Sigrist, Markus;Yoshida, Yutaka;Jessell, Thomas M.;Arber, Silvia
通讯作者：
Arber, Silvia

Expression of the immunoglobulin superfamily cell adhesion molecules in the developing spinal cord and dorsal root ganglion.