ATONAL AND MATH1 AND CNS AND PNS DEVELOPMENT

保守的机制似乎是负责控制神经元， 在脊椎动物和无脊椎动物的发展。无调性（ato）基因是一种 重要的调节开关的弦音器官的形成， 周围神经系统（体壁、关节、听觉结构） 果蝇已经描述了几种与ato同源的脊椎动物。的 小鼠Math1基因与ato基因的同源性最高， 其他老鼠的同源物表达研究显示， 在两个细胞中ato和Math1之间表达模式的保守性 物种：两种基因都在身体的机械传导器官中表达 墙壁关节和听觉系统然而，Math1也被证明是 小脑的外部颗粒层表达和需要。 已证实在中脑中没有ato的表达， 果蝇我已经证明ato确实在果蝇中枢神经系统中表达， 鉴定了对ato的CNS特异性增强。此外，在合作 在Huda Zoghbi博士和Ruth Anne Eatock博士的实验室里， 证明了数学1在脊椎动物耳朵中的功能。因此 这两个基因之间的保守性不仅是结构上的， 从发展的角度来看。我建议进行实验来分析 ato和Math1在其功能不存在的组织中的功能 了解：苍蝇大脑和老鼠内耳。这些研究将 利用果蝇强大的遗传学和 小鼠内耳的胚胎学分析，以及 组织学和分子生物学来解决所提出的问题， 了解神经发育的机制对于 了解可能由扰乱正常 发展，以及设计有效的治疗。

Conserved mechanisms appear to be responsible for the control of neural development in vertebrates and invertebrates. The atonal (ato) gene is an important regulatory switch for chordotonal organ formation in the peripheral nervous system (body wall, joints, auditory structures) of Drosophila. Several vertebrate homologues of ato have been described. The mouse Math1 gene shares the highest homology with ato when compared to the other mouse homologues. Expression studies have shown a striking conservation of the expression pattern between ato and Math1 in the two species: both genes are expressed in mechanotransducing organs of the body wall, joints, and auditory system. However, Math1 has also been shown t be expressed and required for the external granular layer of the cerebellum. No expression has been demonstrated for ato in the mid brain of Drosophila. I have shown that ato is indeed expressed in the fly CNS, and identified a CNS specific enhanced for ato. In addition, in collaboration with Dr. Huda Zoghbi's and Dr. Ruth Anne Eatock's labs, we have demonstrated a function for Math1 in the vertebrate ear. Thus the conservation between the two genes is not only structural, but also functional in developmental terms. i am proposing experiments to analyze the function of ato and Math1 in the tissues where their functions are not understood: the fly brain and the mouse inner ear. These studies will utilize the powerful genetics of Drosophila and the wealth of embryological analysis in the mouse inner ear, as well as techniques for histology and molecular biology to address the questions proposed, Understanding the mechanisms of neural development is important for understanding the pathologies that may result from perturbing normal development, as well as for designing effective treatment.