The role of Ryk/AF6/Eph complexes in neuronal pathfinding/fasciculation

在胚胎发育期间，中枢神经系统中的神经细胞必须找到与其他神经细胞的正确连接。神经细胞寻找合适的伙伴进行连接的过程称为神经元寻路。一旦一些神经细胞建立了正确的连接，其他神经细胞就会附着在这些细胞上，形成神经纤维束。这个过程被称为成束或捆绑。这整个过程对中枢神经系统和大脑的正常发育和功能至关重要。如果神经之间没有正确的连接，信息就不能被接收、处理或发送到身体的器官。我们现在开始发现一些在发育过程中控制神经细胞寻路过程的分子。一段时间以来，人们已经知道称为Eph受体的蛋白质在小鼠头部区域的神经元寻路和发育中起着重要作用。我们现在已经发现另外两种名为Ryk和AF-6的蛋白质能够与Eph受体结合。我们最近制造了缺乏Ryk蛋白的小鼠，这些小鼠的头部发育缺陷与缺乏Eph受体的小鼠的头部缺陷惊人地相似。我们现在希望看到Ryk小鼠是否像缺乏Eph受体的小鼠一样在神经元寻路和成束方面存在缺陷。我们还认为Ryk、Af-6和Eph受体形成了一种蛋白质复合物，可以改变细胞功能。我们现在希望探索这种蛋白质复合物如何做到这一点。

During embryonic development nerve cells in the central nervous system have to find the right connections to make with other nerve cells. The process by which nerve cells find the right partners to make connections with is called neuronal pathfinding. Once some nerve cells have made the right connections, other nerve cells attach to these cells and form bundles of nerve fibres. This process is called fasciculation or bundling. This whole process is vital to the normal development and function of the central nervous system and the brain. Without the right connections between nerves, information could not be received, processed or sent to organs in the body. We are now starting to discover some of the molecules which control the process of nerve cell pathfinding during development. It has been known for some time that proteins called Eph receptors play an important role in neuronal pathfinding and development of the head region in mice. We have now discovered that two other proteins called Ryk and AF-6 are able to bind to Eph receptors. We have very recently created mice which lack the Ryk protein and these mice have defects in their head deveopment strikingly similarto the head defects seen in mice that lack Eph receptors. We now wish to see whether Ryk mice have defects in neuronal pathfinding and fasciculation as do mice lacking Eph receptors. We also think that Ryk, Af-6 and Eph receptors form a protein complex which can modify cell function. We now wish to explore how this protein complex can do this.