Semaphorin 5A is a bifunctional axon guidance cue for axial motoneurons in vivo
Semaphorin 5A is a bifunctional axon guidance cue for axial motoneurons in vivo
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DOI：
10.1016/j.ydbio.2008.11.007
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发表时间：
2009-02-01
影响因子：
2.7
通讯作者：
Beattie, Christine E.
中科院分区：
文献类型：
--
作者：
Hilario, Jona D.;Rodino-Klapac, Louise R.;Beattie, Christine E.
信号素是一大类蛋白质，在神经系统中起着引导轴突的作用。以往的研究表明，Semaphorin 5A(Sema5A)是哺乳动物中脑神经元的双功能轴突引导信号。我们发现斑马鱼Sema5A在运动轴突长出期的肌节中有表达。为了确定Sema5A是否在运动轴向引导中起作用，我们击倒了Sema5A，这导致了两种表型：运动轴突伸入腹侧肌节的延迟和这些运动轴突的异常分支。这两种表型均通过注射全长的大鼠Sema5A mRNA来挽救。然而，单独添加编码SEMA结构域的RNA显著挽救了Sema5A变异体中的分支表型。相反，将编码血栓反应蛋白重复(TSR)结构域的RNA单独添加到Sema5A变形剂中，可以独占地挽救腹侧运动轴突延展的延迟。综上所述，这些数据表明Sema5A是体内脊椎动物运动轴突的双功能轴突引导线索。TSR结构域促进发育中的运动轴突入腹侧肌节的生长，而SEMA结构域介导排斥并阻止这些运动轴突分支进入周围的肌节区域。(C)2008 Elsevier Inc.保留所有权利。
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. (C) 2008 Elsevier Inc. All rights reserved.