Interactions Between IgSF Proteins in Neural Circuit Formation

项目摘要 本申请中概述的实验，以及我们的长期目标，试图填补我们在 了解控制神经回路连接的发育机制。我们与Dr. 斯坦福大学的克里斯托弗·加西亚透露了两个免疫球蛋白超家族亚家族，9人的民主党人和21人的 下沉。这些细胞表面蛋白(CSP)以独特和重叠的模式相互结合，并 表达在果蝇神经系统中的小而独特的神经元亚群上。主要假设 这一应用的基础是dprs和他们的DIP伙伴控制突触基础上的细胞间相互作用。 神经回路中的专一性。我们的创新方法是由DPR-DIP互动组推动的，因为我们能够 系统分析表达相应DPR和DIP伙伴的突触伙伴。与此相关 建议，我收集了初步数据表明，DPR-DIP对介导突触靶向。第一 Aim利用幼虫神经肌肉连接的可达性和不变连接来 了解DPR-DIP对之间的相互作用如何控制运动轴突的形成和靶向 布兰奇。第二个目标的重点是研究DPR-DIP相互作用在轴突生长和轴突生长中的作用。 腹侧神经索的运动神经回路的连接。这些研究将揭示神经支配的基本原理。 电路组装，具体地说，CSP亚家族是如何促成这种特异性的。这些分析将利用 我在果蝇神经发育方面的训练，以及在遗传学、电生理学、显微镜和 形态分析。作为芝加哥大学最近聘用的终身教职助理教授，我将 充分利用跨学科、协作的环境，构建高效、独立的 职业生涯。一个杰出的指导团队，由我的导师Ilaria Rebay博士(芝加哥大学)和联合导师组成， 贝勒医学院的雨果·贝伦博士和本杰明·怀特博士(NIMH)将评估我的进展并 提供反馈。在这个K01奖项下，我将获得额外的技术培训和创造所需的技能 一个严格的、独立的研究计划，并竞争独立的资金，包括R01。这些 经验将为获得终身教职和运营一个成功的、资金充足的实验室奠定基础。

Project Summary The experiments outlined in this application, and our long term goals, seek to fill a large knowledge gap in our understanding of the developmental mechanisms that control neural circuit wiring. Our collaboration with Dr. Christopher Garcia at Stanford revealed two Ig superfamily subfamilies, the 9-member Dprs and 21-member DIPs. These cell surface proteins (CSPs) bind to one other in unique and overlapping patterns and are expressed on small and unique subsets of neurons in the Drosophila nervous system. The primary hypothesis underlying this application is that Dprs and their DIP partners control cell-cell interactions that underlie synaptic specificity in neural circuits. Our innovative approach is fueled by the Dpr-DIP interactome since we are able to systematically analyze synaptic partners that express corresponding Dpr and DIP partners. Relevant to this proposal, I have gathered preliminary data suggesting that a Dpr-DIP pair mediates synaptic targeting. The first aim takes advantage of the accessibility and invariant connections of the larval neuromuscular junction to understand how interactions between this Dpr-DIP pair control the formation and targeting of a motor axon branch. The focus of the second aim is to examine the roles of Dpr-DIP interactions in neurite growth and the wiring of motor circuits in the ventral nerve cord. These studies will uncover basic principles governing neural circuit assembly and specifically, how CSP subfamilies contribute to this specificity. These analyses will utilize my training in Drosophila neural development and expertise in genetics, electrophysiology, microscopy, and morphological analyses. As a recently hired, tenure-track assistant professor at the University of Chicago, I will take full advantage of the interdisciplinary, collaborative environment to build a productive and independent career. An exceptional mentoring team, consisting of my mentor, Dr. Ilaria Rebay (UChicago), and co-mentors, Dr. Hugo Bellen (Baylor College of Medicine) and Dr. Benjamin White (NIMH), will evaluate my progress and provide feedback. Under this K01 award I will gain additional technical training and the skills required to create a rigorous, independent research program and compete for independent funding, including an R01. These experiences will lay the groundwork to obtain tenure and run a successful, well-funded laboratory.