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。我们利用解剖学上分离的和遗传上易懂的嗅觉系统作为一个模型来理解eaffin-A介导的细胞信号的分子机制。随着感觉神经元轴突投射到大脑中的准确位置，基因方法的发展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ephin-as与气味受体作为引导分子协同作用，负责生成精确的地形图。这立即引发了一系列有趣的问题，这些问题具体涉及eaffin-A控制感觉轴突迁移的机制，更广泛地说，可能定义其他细胞中eaffin-A信号的机制。无跨膜结构域的表面分子eaffin-A将细胞外信息转化为有意义的细胞内事件的机制是什么？ 最后，引导分子的性质是什么？这些引导分子既能被ephin-A识别，又能被气味受体识别，从而使它们在像轴突一样精确定位于大脑中的精确位置方面发挥指导作用？

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?