Assembly of the Central Olfactory Networks in Drosophila

描述(申请人提供)：在果蝇和小鼠身上，表达相同受体的嗅觉感受器神经元(ON)向触角叶/嗅球中特定的肾小球目标会聚轴突投射，在中枢神经系统的这一第一个嗅觉结构中创建了气味地图。脊椎动物的二尖瓣/移植细胞和果蝇的触角叶投射神经元(PNS)将树突送入肾小球和轴突，到达高级大脑中心，处理和传递嗅觉信息。我们利用MARCM方法对果蝇PNS进行了系统的克隆分析，发现Pn是由血统和出生顺序预先确定的，与特定的传入ORN轴突突触，从而携带特定的嗅觉信息。此外，根据肾小球分类，三叉神经节在侧角具有典型的轴突分支模式和终末区域，用于进一步处理大脑中的嗅觉信息。侧角是两个中央PN靶点之一。在这项资助中，我们提出了一系列实验，以探索果蝇PNS如何通过将树突定位于特定的肾小球来建立它们的突触连接。我们将研究PN树突状打靶的细胞和发育事件，并利用MARCM方法通过候选基因和正向遗传筛选来鉴定PN树突状打靶的分子和机制。我们还将探索类似于用于指定PN树突状靶向的机制是否也被用于建立其特定的轴突分支模式和终端场。我们尚未发表的初步研究已经表明，某些转录因子和细胞表面蛋白在确定PN树突靶向和指定轴突模式方面的重要性，并证明基于MARCM的镶嵌筛选将使我们能够识别对PN树突靶向特异性至关重要的新基因。这些研究将有助于我们理解一些重要的神经生物学问题，包括神经元命运的指定、树突的引导和靶向，以及嗅觉网络和神经网络总体上的组装逻辑。我们的研究还将深入了解嗅觉信息是如何沿着大脑的中央通路传递和转化的。

DESCRIPTION (provided by applicant): In Drosophila and mice, olfactory receptor neurons (ORNs) expressing the same receptors have convergent axonal projections to specific glomerular targets in the antennal lobe/olfactory bulb, creating an odor map in this first olfactory structure of the CNS. Mitral/mfted cells in vertebrates and antennal lobe projection neurons (PNs) in Drosophila send dendrites into glomeruli and axons to higher brain centers to process and relay the olfactory information. We have made use of the MARCM (Mosaic Analysis with a Repressible Cell Marker) method to perform a systematic clonal analysis of Drosophila PNs, and found that PN's are prespecified by lineage and birth order to synapse with specific incoming ORN axons and therefore to carry specific olfactory information. Further, PNs possess stereotypical axon branching patterns and terminal fields in the lateral horn--one of the two central PN targets--according to glomerular class, for further processing of olfactory information in the brain. In this grant, we propose a series of experiments to explore how Drosophila PNs establish their synaptic connectivity by targeting their dendrites to specific glomeruli. We will study the cellular and developmental events of PN dendritic targeting, and identify molecules and mechanisms for PN dendritic targeting by both candidate gene approaches and a forward genetic screen making use of the MARCM method. We will also explore whether mechanisms similar to those used to specify PN dendritic targeting are also used to establish their specific axon branching patterns and terminal fields. Our unpublished preliminary studies already suggest the importance of certain transcription factor and cell surface proteins in determining PN dendritic targeting and specifying axonal patterning, and prove that a MARCM-based mosaic screen would enable us to identify new genes essential for PN dendritic targeting specificity. These studies will contribute to our understanding of a number of important neurobiological problems, including neuronal fate specification, dendritic guidance and targeting, and the logic of the assembly of the olfactory networks and neural networks in general. Our studies will also provide insight into how olfactory information is transferred and transformed along the central pathways in the brain.