FGF Mediated Guidance of Motor Axons

描述(由申请人提供)：本提案侧重于特定运动神经元亚型引导其适当的肌肉靶点的分子机制。运动轴突向周围的延伸和靶向是哺乳动物神经系统发育的一个基本组成部分，但直接负责这一过程的分子的身份在很大程度上仍然不清楚。初步研究表明，成纤维细胞生长因子基因家族的成员在体外可以诱导运动轴突长出，但在体内对运动轴突导引的作用尚不清楚。这项建议中的实验旨在专门确定成纤维细胞生长因子基因在运动轴突路由中的作用。第一个目标将确定FGFs及其受体在胚胎阶段与运动轴突生长相关的表达模式。目的二将利用成纤维细胞生长因子受体条件突变小鼠来检测由于成纤维细胞生长因子信号的丢失而引起的运动轴突导引的改变。第三个目标将使用鸡脊髓电穿孔来评估成纤维细胞生长因子介导的轴突引导对特定运动神经元亚群的特异性。

DESCRIPTION (provided by applicant): This proposal focuses on the molecular mechanisms that underlie the guidance of specific motor neuron subtypes to their proper muscle targets. The extension and targeting of motor axons to the periphery is a fundamental component of mammalian nervous system development yet the identity of the molecules directly responsible for this process remain largely obscure. Preliminary studies indicate members of the FGF family of genes can induce motor axon outgrowth in vitro, but the effect of FGFs on motor axon guidance in vivo is unknown. The experiments in this proposal are designed is to specifically define the role of FGF genes in motor axon pathfinding. The first aim will define the expression patterns of FGFs and their receptors at embryonic stages relevant to motor axon outgrowth. Aim two will utilize FGF receptor conditional mutant mice to examine the alterations in motor axon guidance that are caused by a loss of FGF signalling. The third aim will use electroporation of chick spinal cord to asses the specificity of FGF mediated axon guidance for specifc subpopulations of motor neurons