Genetic Analysis of Dendrite and Dendritic Filopodia Formation

描述（由申请人提供）： 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中可能受到的干扰至关重要。阿尔茨海默病、脆性X染色体和唐斯综合征中存在树突状形态改变的证据。在某些脊椎动物中，有证据表明树枝状丝状伪足有助于形成树枝状乔木。在哺乳动物中，至少有一些树枝状的丝状伪足可以变成树枝状的刺。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伪足。我们相信，树突和树突丝状伪足的发展，使用一个简单但强大的遗传模型的研究，应该产生更复杂的哺乳动物树突发育的见解。我们的方法结合了一种遗传上适合的生物，果蝇，高分辨率显微镜进行大规模的正向遗传学，以确定基因和信号通路调节树突状细胞的发展。我们也在研究CaMKII的作用，CaMKII是一种与学习和记忆有关的分子，是果蝇树突结构的有效调节剂。由于72%的所有人类神经系统疾病基因在果蝇中发现，本文鉴定的此类基因的直系同源物可能是在哺乳动物树突发育和潜在的人类疾病中发挥作用的候选者。

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 form dendritic arbors. In mammals, at least some dendritic filopodia can become 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 perform large-scale forward genetics to identify genes and signaling pathways regulating dendritic development. We are also investigating the roles of CaMKII, a molecule implicated in learning and memory, as a potent regulator of dendritic structure in Drosophila. As 72% of all human neurological disease genes are found in Drosophila, orthologues of such genes identified herein may be candidates to play a role in mammalian dendrite development and potentially human disease.