Wnt5 and the Patterning of the Olfactory Map

描述（由申请人提供）：地形图是所有感觉系统处理传入信息的手段。因此，了解地形图是如何发展的是神经生物学中的一个紧迫问题。传统上，视网膜轴突向大脑的投射为神经地图的研究提供了模型。然而，近年来，嗅觉地图吸引了越来越多的关注，因为其独特的布线模式。嗅觉神经元对不同气味的反应散布在受体片层中。然而，它们将轴突精确地投射到大脑中的特定目标（肾小球）。由于其独特的连通性，研究嗅觉地图有望产生与视网膜定位地图形成对比的见解。尽管人们对此兴趣浓厚，但嗅觉地图的发展起源仍然是个谜。本实验室的长期目标是以果蝇触角叶为模型系统，阐明神经突导向和嗅觉地图发展的机制。我们的初步数据表明，Wnt 5信号蛋白及其受体，脱轨，是肾小球模式的发展所必需的。在这个提议中，我们假设Wnt 5是早期苍蝇嗅觉地图的组织者，并且特殊的路标细胞表达Wnt 5蛋白。此外，我们假设脱轨作为一种新的细胞外调节Wnt 5。本研究的具体目的是：（1）明确Wnt 5在触角叶发育中的作用和来源。这将通过构建标记路标细胞的特殊标记物和使用标记物对细胞进行详细的表型分析来进行。(2)确定脱轨是Wnt 5的一种新型细胞外调节因子。这将通过脱轨蛋白的结构-功能研究和wnt 5和脱轨基因在触角叶发育过程中的上位性分析来实现。这些实验有望为嗅觉地图发展的最早阶段提供重要的见解。 公共卫生相关性：嗅觉地图对于嗅觉信息的处理至关重要。因此，了解构建地图的机制是神经科学的主要目标。这个区域的建议将有助于解开长期存在的嗅觉地图的发展起源之谜，从而增加我们对大脑如何处理气味的理解。

DESCRIPTION (provided by applicant): Topographic maps are the means by which all sensory systems process afferent information. Hence, understanding how topographic maps develop is a pressing issue in neurobiology. Classically, the projection of retinal axons to the brain has provided a model for the investigation of neural maps. However, in recent years the olfactory map has attracted increasing attention because of its distinct wiring pattern. Olfactory neurons responsive to different odors are interspersed in the receptor sheet. Yet they project their axons with great precision to specific targets (glomeruli) in the brain. Due to its distinct connectivity, studying the olfactory map promises to yield insights that contrast with those of the retinotopic map. Despite intense interests, the developmental origin of the olfactory map remains mysterious. The long-term goal of my laboratory is to elucidate the mechanisms of neurite guidance and olfactory map development, using the Drosophila antennal lobe as a model system. Our preliminary data indicated that the Wnt5 signaling protein and its receptor, Derailed, are required for the development of the glomerular pattern. In this proposal, we hypothesize that Wnt5 is an organizer of the early fly olfactory map and that special guidepost cells express the Wnt5 protein. Furthermore we postulate that Derailed acts as a novel extracellular regulator of Wnt5. Our specific Aims are to: (1) Characterize the function and source of Wnt5 in antennal lobe development. This will be carried out through constructions of special markers that label the guidepost cells and detailed phenotypic analyses of the cells using the markers. (2) Establish that Derailed is a novel extracellular regulator of Wnt5. This will be achieved through a structure-function study of the Derailed protein and epistatic analyses of the wnt5 and derailed genes during antennal lobe development. These experiments are expected to provide critical insights into the earliest stages of olfactory map development. PUBLIC HEALTH RELEVANCE: The olfactory map is essential for the processing of smell information. Thus, understanding the mechanisms that construct the map is a major goal in neuroscience. This AREA proposal will contribute to the unraveling of the long-standing enigma of the developmental origin of the olfactory map, and thus increases our understanding of how the brain processes smell.