Interactions Between IgSF Proteins in Neural Circuit Formation

IgSF 蛋白在神经回路形成中的相互作用

• 批准号: 9371416
• 负责人: Robert Arnulfo Carrillo
• 金额: $ 22.71万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9371416
• 关键词: Autistic Disorder; Axon; Behavior; Binding Proteins; Brain; Cadherins; Cell Communication; Cell Surface Proteins; Cells; Chicago; Collaborations; Data; Dendrites; Development; Down Syndrome Cell Adhesion Molecule; Drosophila genus; Dyslexia; Electrophysiology (science); Face; Feedback; Funding; Genetic; Genetic Screening; Goals; Human; Immunoglobulins; Individual; Interneurons; Knowledge; Laboratories; Link; Malignant Neoplasms; Mediating; Medicine; Mentored Research Scientist Development Award; Mentors; Microscopy; Molecular; Molecular Genetics; Morphology; Motor; Motor Neurons; Mutation; National Institute of Mental Health; Nerve; Nervous system structure; Neurites; Neuromuscular Junction; Neurons; Obesity; Organism; Orthologous Gene; Pathway interactions; Pattern; Phenotype; Physiology; Proteins; Reporter; Research; Resolution; Role; Running; Schizophrenia; Signal Transduction; Specificity; Synapses; System; Testing; Training; Universities; Work; autism spectrum disorder; career; collaborative environment; college; experience; experimental study; human disease; innovation; member; mutant; nervous system disorder; neural circuit; neurite growth; neurodevelopment; neuroregulation; novel; professor; programs; response; skills; tenure track; translational impact

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.

项目摘要 本申请中概述的实验以及我们的长期目标旨在填补我们的知识空白。 了解控制神经回路布线的发育机制。我们与博士的合作。 斯坦福大学的克里斯托弗·加西亚（Christopher Garcia）揭示了两个IG超家族亚家族，即9个成员的多抗和21个成员的 DIP。这些细胞表面蛋白（CSP）以独特和重叠的模式相互结合， 在果蝇神经系统中的小而独特的神经元亚群上表达。主要假设 这一应用的基础是DIPs和它们的DIP配偶体控制细胞间的相互作用，而细胞间的相互作用是突触的基础。 神经回路的特异性。我们的创新方法受到Dpr-DIP相互作用的推动，因为我们能够 系统地分析表达相应Dpr和DIP配偶体的突触配偶体。有关这个 根据这个提议，我已经收集了初步数据，表明Dpr-DIP对介导突触靶向。第一 aim利用幼虫神经肌肉接头的可及性和不变的连接， 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 分支。第二个目标的重点是研究Dpr-DIP相互作用在神经突生长中的作用， 腹神经索中运动回路的布线。这些研究将揭示控制神经系统的基本原理， 电路组装，特别是CSP亚家族如何有助于这种特异性。这些分析将利用 我在果蝇神经发育方面的训练和遗传学、电生理学、显微镜学和 形态学分析作为芝加哥大学最近聘请的终身助理教授，我将 充分利用跨学科的协作环境，建立一个高效和独立的 事业一个特殊的指导团队，包括我的导师，博士Ilaria Rebay（芝加哥大学），和共同导师， 博士Hugo Bellen（贝勒医学院）和Benjamin白色博士（NIMH）将评估我的进展， 提供反馈。在这个K01奖，我将获得额外的技术培训和所需的技能，创造 一个严格的，独立的研究计划，并争取独立的资金，包括R01。这些 这些经验将为获得终身职位和管理一个成功的、资金充足的实验室奠定基础。