Hilario Jona D, Rodino-Klapac Louise R, Wang Chunping, Beattie Christine E
Center for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, 190 Rightmire Hall, 1060 Carmack Rd, Columbus, OH 43210, USA.
Dev Biol. 2009 Feb 1;326(1):190-200. doi: 10.1016/j.ydbio.2008.11.007. Epub 2008 Nov 20.
Semaphorins are a large class of proteins that function throughout the nervous system to guide axons. It had previously been shown that Semaphorin 5A (Sema5A) was a bifunctional axon guidance cue for mammalian midbrain neurons. We found that zebrafish sema5A was expressed in myotomes during the period of motor axon outgrowth. To determine whether Sema5A functioned in motor axon guidance, we knocked down Sema5A, which resulted in two phenotypes: a delay in motor axon extension into the ventral myotome and aberrant branching of these motor axons. Both phenotypes were rescued by injection of full-length rat Sema5A mRNA. However, adding back RNA encoding the sema domain alone significantly rescued the branching phenotype in sema5A morphants. Conversely, adding back RNA encoding the thrombospondin repeat (TSR) domain alone into sema5A morphants exclusively rescued delay in ventral motor axon extension. Together, these data show that Sema5A is a bifunctional axon guidance cue for vertebrate motor axons in vivo. The TSR domain promotes growth of developing motor axons into the ventral myotome whereas the sema domain mediates repulsion and keeps these motor axons from branching into surrounding myotome regions.
信号素是一大类蛋白质，在整个神经系统中发挥作用以引导轴突。先前已有研究表明，信号素5A（Sema5A）是哺乳动物中脑神经元的双功能轴突导向信号。我们发现，斑马鱼的sema5A在运动轴突生长期间在体节中表达。为了确定Sema5A是否在运动轴突导向中发挥作用，我们敲低了Sema5A，结果出现了两种表型：运动轴突向腹侧体节延伸延迟以及这些运动轴突的异常分支。通过注射全长大鼠Sema5A mRNA可挽救这两种表型。然而，单独添加编码信号素结构域的RNA可显著挽救sema5A morphants中的分支表型。相反，单独将编码血小板反应蛋白重复（TSR）结构域的RNA添加到sema5A morphants中只能挽救腹侧运动轴突延伸的延迟。这些数据共同表明，Sema5A是体内脊椎动物运动轴突的双功能轴突导向信号。TSR结构域促进发育中的运动轴突向腹侧体节生长，而信号素结构域介导排斥作用，防止这些运动轴突分支进入周围的体节区域。
