Assembly of the Central Olfactory Networks in Drosophila

描述（由申请人提供）：在果蝇和小鼠中，表达相同受体的嗅觉受体神经元（ORN）具有会聚轴突投射至触角叶/嗅球中的特定肾小球靶点，在CNS的第一嗅觉结构中创建气味图。脊椎动物的二尖瓣/移行细胞和果蝇的触角叶投射神经元（projection neurons，PNs）将树突送入肾小球和轴突到高级脑中心来处理和传递嗅觉信息。我们利用MARCM（Mosaic Analysis with a Repressible Cell Marker）方法对果蝇PN进行了系统的克隆分析，发现PN是由谱系和出生顺序预先指定的，与特定的传入ORN轴突突触，因此携带特定的嗅觉信息。此外，PN具有刻板的轴突分支模式和终端领域的侧角-两个中央PN目标之一-根据肾小球类，进一步处理嗅觉信息在大脑中。在这项研究中，我们提出了一系列的实验，以探讨果蝇PN如何建立他们的突触连接的树突靶向特定的肾小球。我们将研究PN树突状靶向的细胞和发育事件，并确定PN树突状靶向的候选基因方法和正向遗传筛选利用MARCM方法的分子和机制。我们还将探讨是否机制类似于那些用于指定PN树突状靶向也被用来建立其特定的轴突分支模式和终端领域。我们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图案中的重要性，并证明基于MARCM的镶嵌筛选将使我们能够识别PN树突靶向特异性所必需的新基因。这些研究将有助于我们理解一些重要的神经生物学问题，包括神经元的命运规范，树突状细胞的指导和靶向，以及嗅觉网络和神经网络的组装逻辑。我们的研究也将提供嗅觉信息是如何沿着大脑中的中枢通路进行沿着和转换的。

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 Our unpublished preliminary studies already suggest the importance of certain transcription factor and cell surface proteins in determining PN dendritic targeting and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.