SEMAPHORINS E AND H AND GROWTH CONE GUIDANCE

描述（来自申请人摘要的逐字描述）：正确接线 神经系统的连接需要轴突延伸相对较长的距离， 在发育中的胚胎内的距离，并连接到非常具体的目标。 延伸轴突的导向是由一种 引诱剂和驱避剂的数量。的 识别这些引导线索将帮助我们了解如何正确 以及在被损坏后如何重建 在以后的生活中 信号蛋白是一个至少有10-15个成员的信号分子家族 在任何高等脊椎动物中。家族中的一员， （小鼠sema-D，人sema-III）是一种强大的感觉神经元驱避剂， 体外当这种基因在小鼠中发生突变时，外周感觉轴突束 严重地去束化并进入它们通常会避开的区域。 大多数其他脊椎动物信号蛋白的功能是未知的。我们做了一个 对胚胎中sema-E和sema-H的分布进行了详细的检查 小妞然后，我们将它们的表达模式与轴突的轨迹进行了比较， 有这两种信号分子受体的纤维束。初步 在胚胎小鼠中进行了比较。这些描述性研究表明， sema-E和sema-H在发育过程中可能作为轴突导向线索。 这一点得到了以下发现的进一步支持，即sema-E排斥交感神经轴突， 在体外试验中吸引皮层轴突。 我们的目标是测试是否sema-E或sema-H作为轴突导向线索 在发展过程中。这将通过确定突变是否 这两个基因中的任何一个通过小鼠中的同源重组扰乱了 在体内延伸轴突的轨迹。

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.