Genetic Analysis of Dendrite and Dendritic Filopodia Formation

描述(申请人提供)：在大脑中，大多数信息处理物理上发生在神经元树突上。了解树突和树突结构是如何发展和功能的，对于理解正常认知以及人类认知障碍和发育迟缓综合征中可能受到的干扰是至关重要的。阿尔茨海默病、脆性X综合征和唐斯综合征中存在树突状细胞形态改变的证据。在一些脊椎动物中，有证据表明树状丝状足有助于确定树状乔木的形状。在哺乳动物中，一些树突丝状足被证明是树突棘的前体。在果蝇中，我们能够在光学透明的完好动物身上看到树突和树突丝状足。我们相信，使用一个简单但强大的遗传模型来研究树突和树突丝状足的发育，应该会对更复杂的哺乳动物树突发育产生深刻的见解。我们的方法结合了遗传上可服从的有机体--果蝇--与高分辨率显微镜相结合，以分析和识别新的基因或以前未知的调节神经元树突的基因。我们希望从这项研究中找出调节神经元树突发育的信号分子和信号通路。由于72%的人类神经系统疾病基因可以在果蝇中找到，因此这些基因的同源基因可能在哺乳动物树突发育中发挥作用，也可能在人类神经发育障碍中发挥作用。

DESCRIPTION (provided by applicant): In the brain, most information processing physically occurs on neuronal dendrites. Understanding how dendrites and dendritic structure develop and function is critical to understanding normal cognition and what may be perturbed in human cognitive disorders and retardation syndromes. Evidence for altered dendritic morphology exists in Alzheimers, Fragile X, and Downs syndrome. In some vertebrates there is evidence that dendritic filopodia help determine the shape of dendritic arbors. In mammals, some dendritic filopodia have been shown to be precursors to dendritic spines. In Drosophila, we are able to visualize dendrites and dendritic filopodia in optically transparent intact animals. We believe the study of dendrites and dendritic filopodia development using a simple but powerful genetic model, should yield insights into more complex mammalian dendrite development. Our approach combines a genetically amenable organism, Drosophila, with high-resolution microscopy to analyze and identify either new genes or genes not previously known to regulate neuronal dendrites. From this proposal we hope to identify signaling molecules and pathways that regulate neuronal dendrite development. As 72% of all human neurological disease genes can be found in Drosophila, orthologues of such genes identified herein may be candidates to play a role in mammalian dendrite development and potentially human neurodevelomental disorders as well.