FGF Mediated Guidance of Motor Axons

描述（由申请人提供）：该提案侧重于指导特定运动神经元亚型到达其适当肌肉靶点的分子机制。运动轴突向外周的延伸和靶向是哺乳动物神经系统发育的基本组成部分，但直接负责这一过程的分子的身份在很大程度上仍不清楚。初步研究表明，FGF基因家族的成员可以在体外诱导运动轴突生长，但FGF对体内运动轴突导向的作用尚不清楚。本实验旨在明确FGF基因在运动轴突寻路中的作用。第一个目标是确定FGF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FGF受体条件突变小鼠来检查由FGF信号传导丢失引起的运动轴突引导的改变。第三个目标是利用鸡脊髓电穿孔来评估FGF介导的轴突导向运动神经元特定亚群的特异性

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