GENETICS OF NEURONAL RECOGNITION IN DROSOPHILA

在中线对称的神经系统中，相当数量的神经元将轴突从一侧投射到另一侧。尽管已经发现了几种控制轴突是否穿过中线的分子，但直到最近，人们仍然不知道这些相同的轴突是如何选择合适的途径交叉的，这一选择对神经系统功能至关重要。在果蝇胚胎中，穿过中线脱轨(DRL)受体的轴突表达在所有穿过AC中线的神经元的生长锥体和轴突上，并作为PC中存在的排斥配体的引导受体。这个项目的目标是了解如何通过测试一系列缺失和氨基酸替换来识别信号所需的DRL指南。DRL功能的一个重要特征是在生长锥体和轴突离开AC后下调。利用体内试验，将确定其下调所需的DRL区域。DRL的配体，以及DRL受体在生长锥中作用的信号转导途径的组成部分，将通过遗传和生化手段进行鉴定。可能还有其他引导受体和配体与Dr1协同作用，在轴突穿过中线时对轴突进行分类，这种分子的一个主要候选者是Drl2，它是Dr1家族的另一个成员，显然表达在PC神经元中。Drl2在连合选择中的作用将通过错误表达研究和产生基因突变来确定。

In nervous systems with symmetry about the midline, a substantial number of neurons project axons from one side to the other. Although several molecules have been identified that control whether or not an axon crosses the midline, until recently it has remained unknown how these same axons manage to choose the appropriate pathway in which to cross, a choice that is critical for nervous system function. In the Drosophila embryo, axons cross the midline Derailed (Drl) receptor tyrosine kinase is expressed on the growth cones and axons of all neurons that traverse the midline in the AC and acts as a guidance receptor for a repellant ligand present in the PC. The goal of this project is to understand how the Drl guidance required for signaling will be identified by testing a series of deletions and amino acid substitutions. A critical feature of Drl function is its down-regulation in growth cones and axons after they leave the AC. Using an in vivo assay, the regions of Drl required for its down regulation will be defined. DRL's ligand, as well as components of the signal transduction pathway through which the Drl receptor acts in the growth cone, will be identified using genetic and biochemical. There are likely to be other guidance receptors and ligands acting in concert with Dr1 to sort axons as they traverse the midline, and a prime candidate for such a molecule is Drl2, another member of the Dr1 family apparently expressed in PC neurons. The role of Drl2 in commissure choice will be defined by misexpression studies and by generating mutations in the gene.