The Role of Wnt2 in Drosophila Antenna Lobe Development

描述（申请人提供）：气味的感知需要嗅觉信息在大脑中被系统地组织起来。这个组织被称为嗅觉图，由嗅觉受体神经元和它们的突触后目标之间的精确连接组成。然而，负责嗅觉图谱形成的分子机制尚不清楚。我发现Wnt2是保守的Wnt家族分泌蛋白的一员，对于果蝇AL的组织是必需的，AL是一种嗅觉结构，由嗅觉受体神经元（嗅觉受体神经元）组成，与投射神经元突触。在每个All中，表达给定气味受体基因的轴突聚集在单个肾小球上。wnt2基因通过组织AL，在确定果蝇嗅觉图谱的精确连通性方面发挥着重要作用。缺乏功能性wnt2基因的动物表现出严重紊乱的较小的AL。特异性ORN的标记显示，ALs中有很大比例的ORN轴突缺失，肾小球结构严重退化。过表达Wnt2诱导AL连接中异位突触的形成，这种结构通常由轴突束组成。我假设Wnt2既调节嗅觉受体神经元轴突引导，也调节天线瓣内的突触分化。本研究的目的是通过确定Wnt2的细胞功能、发育要求和表达Wnt2的细胞类型来研究Wnt2在嗅觉图谱形成中的作用。

DESCRIPTION (provided by applicant): The perception of odors requires olfactory information to be systematically organized in the brain. This organization, termed the olfactory map, consists of precise connections between olfactory receptor neurons and their postsynaptic targets. The molecular mechanisms responsible for olfactory map formation, however, is not well understood. I have discovered that Wnt2, a member of the conserved Wnt family of secreted proteins, is necessary for the organization of the Drosophila AL, an olfactory structure composed of olfactory receptor neurons (ORNs) that synapse upon projection neurons. In each All, axons expressing a given odorant receptor gene converge on a single glomerulus. The wnt2 gene plays a powerful role in specifying the precise connectivity of the Drosophila olfactory map by organizing the AL. Animals lacking a functional wnt2 gene exhibit severely disorganized, smaller ALs. Labeling of specific ORNs reveals that a large proportion of ORN axons are missing from the ALs and the structures of the glomeruli are severely degraded. Overexpression of Wnt2 induces the formation of ectopic synapses in the AL commissure, a structure normally composed of tracts of axons. I hypothesize that Wnt2 regulates both olfactory receptor neuron axon guidance and synaptic differentiation within the antenna lobe. The aim of this proposal is to investigate the role of Wnt2 in olfactory map formation by determining its cellular function, developmental requirements, and the cell types that express Wnt2.