Genetic Analysis of Dendrite and Dendritic Filopodia Formation

描述（由申请人提供）：在大脑中，大多数物理信息处理发生在神经元树突上。了解树突和树突结构如何发育和功能对于理解正常认知以及人类认知障碍和发育迟缓综合征可能受到的干扰至关重要。树突形态改变的证据存在于阿尔茨海默氏症、脆性X染色体和唐氏综合症中。在一些脊椎动物中，有证据表明树突丝状足有助于决定树突乔木的形状。在哺乳动物中，一些树突丝状足已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整动物中可视化树突和树突丝状足。我们相信，利用一种简单但功能强大的遗传模型对树突和树突丝状足的发育进行研究，将有助于了解更复杂的哺乳动物树突发育。我们的方法结合了一种遗传上可适应的生物，果蝇，用高分辨率显微镜来分析和鉴定新的基因或以前不知道的基因来调节神经元树突。从这个建议，我们希望确定信号分子和途径，调节神经元树突的发展。由于在果蝇中可以发现72%的人类神经系统疾病基因，因此本文鉴定的这些基因的同源物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.