Identification of homologues of the Commissureless protein

描述（由申请人提供）：神经系统左右两侧之间的神经连接对协调和独立运动至关重要。脊髓中这些连接的破坏会导致脊柱弯曲（脊柱侧凸），这种情况会限制身体活动，引起疼痛并导致呼吸问题。在胚胎发育过程中，中枢神经系统（CNS）中的许多生长神经会决定是否向另一侧转移。它们通过感知环境中的导航线索，利用细胞表面被称为受体的特殊蛋白质来做到这一点。通过控制哪些受体到达细胞表面，神经元可以控制它们是否能对环境中的不同信号做出反应。人们对这个过程是如何控制的了解甚少。在果蝇中，“无通讯”或通讯突变体的左右两侧之间根本没有神经连接。Comm蛋白控制一类被称为Robos的受体能否到达细胞表面。在人类中，Robo受体的遗传变异与脊柱侧凸和发育性阅读障碍等多种疾病有关。迄今为止，在昆虫之外还没有发现comm基因。本提案旨在通过在果蝇中使用定义明确的测定来测试来自其他物种的候选基因。识别来自其他物种的comm基因将为研究受体定位的控制开辟新的途径，并增加我们对胚胎中神经如何准确地进行长距离导航的理解。它也可能有助于确定脊柱侧凸和其他神经连接模式改变的疾病的新位点。

DESCRIPTION (provided by applicant): Nerve connections between the left and right hand sides of the nervous system are critically important for coordinated and independent movements. Disruption of these connections in the spinal cord can lead to curvature of the spine (scoliosis), a condition that can restrict physical activity, cause pain and lead to problems breathing. Many growing nerves in the central nervous system (CNS) make a decision whether or not to cross to the other side during embryonic development. They do this by sensing navigational cues in their environment, using specialized proteins on their cell surface known as receptors. Controlling which receptors make it to the cell surface allows neurons to control whether or not they can respond to different cues in their environment. Understanding how this process is controlled is poorly understood. In the fruit fly, "commissureless" or comm mutants have no nerve connections between their left and right sides at all. The Comm protein controls whether or not a class of receptors called Robos can make it to the cell surface. In humans, genetic variants of Robo receptors have been implicated in such diverse conditions as scoliosis and developmental dyslexia. To date, comm genes have not been found outside of insects. This proposal aims to test candidate genes from other species by using well-defined assays in fruit flies. Identification of comm genes from other species will open new avenues to studying control of receptor localization, and add to our understanding of how nerves accurately navigate long distances in the embryo. It may also help identify a novel locus for scoliosis and other disorders in which nerve wiring patterns are altered. PUBLIC HEALTH RELEVANCE: The commissureless gene plays a central role in nerve navigation at the CNS midline of fruit flies, yet vertebrate homologues have not been identified. This proposal aims to identify functional homologues, increasing our understanding of spinal cord development.