GENETIC ANALYSIS OF FUNCTION OF EPH RECEPTORS & LIGANDS

Eph受体酪氨酸激酶大家族负责一系列独特的细胞功能，包括细胞迁移，细胞分离和轴突引导。我们采用解剖分离和遗传上容易的嗅觉感觉系统作为模型来理解ephrin- a介导的细胞信号传导的分子机制。随着遗传学方法的发展，感觉神经元的轴突投射到大脑的精确位置，使我们能够解剖这些复杂而精确的神经元迁移。我们的数据表明，生长中的感觉轴突上的ephrin- a与气味受体作为指导分子协同作用，负责生成精确的地形图。这立即提出了一系列有趣的问题，具体解决了ephrin-A控制感觉轴突迁移的机制，并更广泛地定义了其他细胞中ephrin-A信号传导的机制。ephrin-A是一种没有跨膜结构域的表面分子，它将细胞外信息转导成有意义的细胞内事件的机制是什么？ephrin-A信号引导轴突到达离散的地形位置的下游通路是什么？

The large family of Eph receptor tyrosine kinases is responsible for a unique array of cellular functions including cell migration, cell segregation, and axon guidance. We have employed the anatomically segregated and genetically facile olfactory sensory system as a model to understand the molecular mechanisms of ephrin-A-mediated cell signaling. The development of genetic approaches to visualize axons from sensory neurons as they project to precise locations in the brain has permitted us to dissect these complex, yet precise neuronal migrations. Our data suggest that ephrin-As on the growing sensory axon act in concert with odorant receptors as guidance molecules responsible for the generation of a precise topographic map. This immediately poses a series of interesting questions that specifically address the mechanism by which ephrin-As control sensory axon migration and more generally may define the mechanisms of ephrin-A signaling in other cells. What is the mechanism by which ephrin-A, a surface molecule without a transmembrane domain, transduces extracellular information into meaningful intracellular events? What are the downstream pathways through which ephrin-A signals to guide axons to discrete topographic locations? Finally, what is the nature of the guidance molecules recognized by both ephrin-A and the odorant receptors to allow them an instructive role in targeting like axons to precise loci in the brain?