Development and function of an adult locomotion circuit in Drosophila

描述（由申请人提供）：动物运动需要运动神经元的协调放电，从而触发附肢（如腿）中肌肉的收缩。此外，协调需要来自位于附肢的感觉神经元的反馈。为了了解功能性运动神经元回路是如何形成的，本项目将研究成年果蝇用于行走的运动回路的发育和功能。将使用新的遗传学和分子生物学方法来破译赋予每个运动神经元其特定身份所需的组合转录因子代码。一旦确定，将分析干扰少量运动神经元对行走的影响。最后，从机械感觉器官在腿部的感觉反馈的作用的特点。总之，这些研究将为一种新的模型遗传系统奠定基础，该系统用于研究遗传上易于控制的动物的运动回路，与其幼虫对应物不同，这种动物使用附属物进行运动。 公共卫生相关性：动物的运动需要运动神经元的协调放电，从而触发附肢（如腿）的肌肉收缩。本计画将探讨果蝇成虫行走所使用的运动回路的发展与功能。该模型系统的使用将有助于破译协调运动所需的基因和神经元，因此，最终治疗由神经退行性疾病和衰老引起的运动神经元相关功能障碍。

DESCRIPTION (provided by applicant): Animal locomotion requires the coordinated firing of motor neurons that trigger the contraction of muscles in the appendages, such as the legs. In addition, coordination requires feedback from sensory neurons located in the appendages. To understand how functional motor neuron circuits form, this project will investigate the development and function of the motor circuit used by the adult fruit fly for walking. The combinatorial transcription factor code required to give each motor neuron its particular identity will be deciphered using both novel genetic and molecular biology approaches. Once identified, the consequences on walking of perturbing small numbers of motor neurons will be analyzed. Finally, the role of sensory feedback from mechanosensory organs in the legs will be characterized. Together, these studies will lay the ground work for a new model genetic system for studying motor circuits in a genetically tractable animal that, unlike its larval counterpart, uses appendages for locomotion. PUBLIC HEALTH RELEVANCE: Animal locomotion requires the coordinated firing of motor neurons that trigger the contraction of muscles in the appendages, such as the legs. This project will investigate the development and function of the motor circuit used by the adult fruit fly for walking. The use of this model system will help to decipher the genes and neurons required for coordinated locomotion and, therefore, the eventual treatment of motor neuron-related dysfunction resulting from neurodegenerative diseases and aging.