Development and function of an adult locomotion circuit in Drosophila

 描述(申请人提供)：神经元之间的形态多样性是巨大的，对它们的功能至关重要，但关于这种多样性是如何遗传编码的，我们的知识中仍然有许多空白。与脊椎动物运动神经元一样，黑腹果蝇的运动神经元在附件中正确的肌肉纤维上建立高度特异的突触，并在中枢神经系统(CNS)中形成高度定型的树突。在之前的资助时期，这种运动神经元形态的多样性是在单细胞水平上为47个运动神经元定义的，这些运动神经元支配和控制果蝇每条成年腿的运动。此外，一组转录因子的特征是以组合的方式决定七个运动神经元的形态，这些神经元都来自相同的神经母细胞干细胞。另外定义了一组在干细胞谱系中以时间不同的方式表达的因子，该干细胞谱系产生了28个运动神经元。基于这些发现，下一个资助期的一个目标是通过测试组合TF码是如何在有丝分裂后神经元中建立的，测试它们受到神经母细胞早期作用因素的调节的假设。第二个目标是确定在有丝分裂后运动神经元中受转录因子调控的TE基因和通路，这些基因和通路控制着它们在成年腿中的突触特异性和中枢神经系统中的树突结构。将使用遗传筛选和分子方法相结合的方法。第三个长期目标是确定成人腿部肌肉如何与运动神经元协调发展，以建立突触特异性。使用一种高度定量的方法来分析苍蝇行走，将分析干扰这些神经元和/或肌肉的发育对行走行为的影响。总体而言，这些研究将把一组高度定型的神经元的发育与它们在特定成人行为中的功能联系起来。

 DESCRIPTION (provided by applicant): The morphological diversity among neurons is enormous and critical to their function, yet many gaps in our knowledge remain concerning how this diversity is genetically encoded. As with vertebrate motor neurons, the motor neurons of Drosophila melanogaster establish highly specific synapses on the correct muscle fibers in the appendages and also elaborate highly stereotyped dendritic arbors in the central nervous system (CNS). In the previous funding period, this diversity of motor neuron morphology was defined at the single cell level for the 47 motor neurons that innervate and control the movements of each of the adult legs of Drosophila. Further, sets of transcription factors were characterized that act in a combinatorial manner to dictate the morphologies of seven motor neurons, all derived from the same neuroblast stem cell. An additional set of factors was defined that are expressed in a temporally distinct manner in a stem cell lineage that gives rise to 28 motor neurons. Based on these findings, one goal for the next funding period is to determine how combinatorial TF codes are established in post-mitotic neurons, by testing the hypothesis that they are regulated by factors acting earlier in the neuroblast. A second goal is to identify te genes and pathways regulated by TFs in post-mitotic motor neurons that control their synaptic specificity in the adult legs and dendritic architecture in the CNS. A combination of genetic screens and molecular approaches will be used. A third long term goal is to determine how the adult leg muscles develop coordinately with motor neurons to establish synaptic specificity. Using a highly quantitative method for analyzing fly walking, the consequences on walking behavior by perturbing the development of these neurons and/or muscles will be analyzed. In general, these studies will link the development of a highly stereotyped set of neurons to their function in a specific adult behavior.