GENETICS OF NEURONAL RECOGNITION IN DROSOPHILA

在关于中线对称的神经系统中，大量神经元将轴突从一侧投射到另一侧。虽然已经确定了几种控制轴突是否穿过中线的分子，但直到最近，仍然不知道这些轴突如何选择合适的通路来穿越，这对神经系统功能至关重要。在果蝇胚胎中，轴突穿过中线脱轨（Drl）受体酪氨酸激酶在生长锥和穿过AC中线的所有神经元的轴突上表达，并充当PC中存在的排斥配体的指导受体。该项目的目标是了解如何通过测试一系列缺失和氨基酸取代来鉴定信号传导所需的Drl指导。Drl功能的一个关键特征是其在生长锥和轴突离开AC后的下调。使用体内测定，将定义其下调所需的Drl的区域。DRL的配体，以及信号转导途径的组成部分，通过它的Drl受体在生长锥中的作用，将被确定使用遗传和生物化学。很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，而这种分子的主要候选者是Dr12，Dr1家族的另一个成员，显然在PC神经元中表达。Drl2在连合选择中的作用将通过错误表达研究和通过在基因中产生突变来定义。

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.