EphB1 signaling in retinal axon guidance

EphB1信号在视网膜轴突引导中的作用

• 批准号: 7129022
• 负责人: TIMOTHY J PETROS
• 金额: $ 4.53万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7129022
• 关键词: Sindbis virus; axon; biological signal transduction; calcium flux; developmental neurobiology; electroporation; embryo /fetus tissue /cell culture; embryogenesis; ephrins; growth cones; immunocytochemistry; laboratory mouse; molecular /cellular imaging; neurogenesis; neuronal guidance; optic chiasmas; predoctoral investigator; protein protein interaction; receptor binding; receptor expression; retina; retinal ganglion; tissue /cell culture; transfection /expression vector

DESCRIPTION (provided by applicant): The proposed research utilizes in vitro and in vivo assays to identify downstream signaling mechanisms of a specific receptor-ligand (EphB1-ephrin-B2) interaction that patterns binocular vision by mediating repulsion of ventrotemporal (uncrossed) retinal axons at the optic chiasm. To demonstrate the specificity and sufficiency of this interaction, EphB1 and EphB2 will be introduced into EphB1 null retinal explants in vitro and embryonic retinae in vivo, and axon projections and responses to ephrin-B2 substrates will be characterized. EphB1 can activate numerous downstream signaling pathways in heterologous systems, but it is unknown which of these are biologically relevant. A series of experiments will characterize the role of growth cone calcium transients in mediating EphB1 repulsion from ephrin-B2. In tandem, additional studies will use pharmacological methods to identify which pathways are required for EphB1-mediated repulsion from ephrin-B2. Lastly, a series of mutations in the EphB1 receptor will be introduced in these same assays to reveal which domains are responsible for transducing EphB1 activation into repulsion. These experiments will increase our knowledge in the fields of axon guidance and growth cone dynamics.

描述（由申请人提供）：拟议的研究利用体外和体内试验来确定特定受体-配体（EphB1-ephrin-B2）相互作用的下游信号机制，该相互作用通过介导视交叉处腹颞（未交叉）视网膜轴突的排斥来调节双眼视觉。为了证明这种相互作用的特异性和充充性，研究人员将EphB1和EphB2引入到体外EphB1缺失的视网膜外植体和体内胚胎视网膜中，并对轴突的投射和对ephrin-B2底物的反应进行表征。EphB1可以在异源系统中激活许多下游信号通路，但尚不清楚其中哪些与生物学相关。一系列的实验将表征生长锥钙瞬态在介导EphB1排斥ephrin-B2中的作用。与此同时，进一步的研究将使用药理学方法来确定ephb1介导的排斥ephrin-B2所需的途径。最后，将在这些相同的实验中引入一系列EphB1受体突变，以揭示哪些结构域负责将EphB1激活转导为排斥。这些实验将增加我们在轴突引导和生长锥动力学领域的知识。