SEMAPHORINS E AND H AND GROWTH CONE GUIDANCE

描述(逐字摘自申请者摘要)：正确的接线 神经系统的结合需要轴突延伸到相对较长的距离 在发育中的胚胎内的距离，并连接到非常特定的目标。 伸展轴突的导向受多种突起的分布控制 在它们生长的环境中的引诱剂和驱避剂。这个 识别这些指导线索将帮助我们理解如何正确 接线完成了，也许在损坏后如何才能重建 在以后的生活中。 信号素是一个至少有10-15个成员的信号分子家族 在任何给定的高等脊椎动物中。家庭中的一名成员，小鸡崩溃-1 (小鼠SEMA-D，人SEMA-III)是一种强大的感觉神经元驱避剂 体外培养。当这个基因在小鼠身上发生突变时，周围的感觉神经轴突会收缩 被严重剥离并进入它们通常会避开的区域。 大多数其他脊椎动物信号素的功能尚不清楚。我们已经做了一个 SEMA-E和SEMA-H在胚胎中分布的详细观察 小鸡。然后我们将它们的表达模式与轴突的轨迹进行了比较 有这两个信号分子受体的神经束。初赛 已经在胚胎小鼠身上进行了比较。这些描述性研究表明 提示SEMA-E和SEMA-H在发育过程中可作为轴突的引导信号。 SEMA-E排斥交感神经轴突的发现进一步支持了这一点 在体外测试中吸引皮质轴突。 我们的目标是测试SEMA-E或SEMA-H是否作为轴突引导线索 在开发过程中。这将通过确定突变是否 这两个基因中的任何一个在小鼠中通过同源重组扰乱了 活体内轴突延伸的轨迹。

DESCRIPTION (Verbatim from the Applicant's Abstract): The correct wiring together of the nervous system requires that axons extend over relatively long distances within the developing embryo and connect to very specific targets. The guidance of extending axons is controlled by the distribution of a variety of attractants and repellents in the environment through which they grow. The identification of these guidance cues will help us understand how correct wiring is achieved, and perhaps how it can be reestablished after being damaged later in life. The semaphorins are a family of signaling molecules with at least 10-15 members in any given higher vertebrate. One member of the family, chick collapsin-1 (mouse sema-D, human sema-III) is a powerful repellent of sensory neurons in vitro. When this gene is mutated in the mouse, peripheral sensory axon tracts are grossly defasciculated and enter into regions they would normally avoid. The functions of most other vertebrate semaphorins are unknown. We have made a detailed examination of the distributions of sema-E and sema-H in the embryonic chick. We then compared their expression patterns to the trajectories of axon tracts that have receptors for these two signaling molecules. A preliminary comparison has been made in embryonic mice. These descriptive studies suggest that sema-E and sema-H could act as axonal guidance cues during development. This is further supported by findings that sema-E repels sympathetic axons and attracts cortical axons in in vitro assays. Our objective is to test whether sema-E or sema-H act as axonal guidance cues during development. This will be accomplished by determining whether mutating either of these two genes by homologous recombination in mice perturbs the trajectories of extending axons in vivo.