Using Drosophila to investigate the roles of conserved IgSF proteins in neuronal differentiation and axon guidance.

使用果蝇研究保守 IgSF 蛋白在神经元分化和轴突引导中的作用。

• 批准号: 346134-2012
• 负责人: vanMeyel, Donald
• 金额: $ 2.48万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=549667
• 关键词: Using; Drosophila; investigate; roles; conserved

The ability of the brain to function properly relies upon patterned development of neurons and the controlled establishment of synaptic connections. The overall objective of our research program is to use the Drosophila model system to understand these processes at a molecular and cellular level. We are investigating how extrinsic signals influence the differentiation of neurons and the guidance of axons via three transmembrane proteins of the immunoglobulin superfamily (IgSF) known as Ihog, Boi and Tutl. In the previous 3-yr term of this Discovery Grant, students in the van Meyel lab have made exciting discoveries that implicate Ihog, Boi and Tutl as key regulators of neuronal differentiation and/or axon guidance. These IgSF proteins are conserved in other species including mammals, and they are comprised of ectodomains with Ig-like and fibronectin type III repeats, a transmembrane domain, and a cytoplasmic tail. We have found recently that Ihog and Boi are functionally redundant and essential for signaling via the Hedgehog (Hh) pathway. Hh is an important determinant of neuronal differentiation in the retina, spinal cord, brain, and many other cell types. We have also found that Tutl is important patterned growth and guidance of axons and dendrites, but the mechanism of action of Tutl remains completely mysterious. The specific objectives of this research program are to: 1) determine how Ihog and Boi participate in the Hedgehog signaling pathway, 2) characterize new functions for Ihog and Boi in axon guidance and Hh transport and 3) investigate the role of Tutl in axon guidance. This Discovery Grant builds on the foundation of research funded over the previous 3-yr period to identify novel axon guidance molecules. Our innovative research program provides excellent conceptual and technical training for students, where our long-term goal is to explain at a molecular level the principles upon which neural circuits in the brain are built and assembled during development.

大脑正常运作的能力依赖于神经元的模式化发育和突触连接的受控建立。我们研究计划的总体目标是使用果蝇模型系统在分子和细胞水平上理解这些过程。我们正在研究外部信号如何影响神经元的分化和轴突的指导通过三个跨膜蛋白的免疫球蛋白超家族（IgSF）被称为Ihog，Boi和Tutl。在这个发现补助金的前3年学期中，货车Meyel实验室的学生已经取得了令人兴奋的发现，这些发现涉及Ihog，Boi和Tutl作为神经元分化和/或轴突指导的关键调节因子。这些IgSF蛋白在包括哺乳动物在内的其他物种中是保守的，并且它们由具有Ig样和纤连蛋白III型重复序列的胞外域、跨膜结构域和胞质尾区组成。我们最近发现Ihog和Boi在功能上是冗余的，并且对于通过Hedgehog（Hh）途径的信号传导是必需的。Hh是视网膜、脊髓、脑和许多其他细胞类型中神经元分化的重要决定因素。我们还发现，Tutl是重要的模式化生长和指导轴突和树突，但Tutl的作用机制仍然完全神秘。本研究计划的具体目标是：1）确定Ihog和Boi如何参与Hedgehog信号通路，2）表征Ihog和Boi在轴突导向和Hh转运中的新功能，3）研究Tutl在轴突导向中的作用。这项发现补助金建立在前3年资助的研究基础上，以确定新的轴突导向分子。我们的创新研究计划为学生提供了优秀的概念和技术培训，我们的长期目标是在分子水平上解释大脑神经回路在发育过程中建立和组装的原则。