Eberhart J, Swartz M, Koblar S A, Pasquale E B, Tanaka H, Krull C E
Division of Biological Sciences, University of Missouri-Columbia, Columbia, 65211, USA.
Dev Neurosci. 2000;22(3):237-50. doi: 10.1159/000017446.
During neural development, spinal motor axons extend in a precise manner from the ventral portion of the developing spinal cord to innervate muscle targets in the limb. Although classical studies in avians have characterized the cellular interactions that influence motor axon pathfinding to the limb, less is known about the molecular mechanisms that mediate this developmental event. Here, we examine the spatiotemporal distributions of the EphA4 receptor tyrosine kinase (RTK) and its cognate ligands, ephrin-A2 and ephrin-A5, on motor neurons, their axons and their pathways to the avian hindlimb to determine whether these molecules may influence axonal projections. The expression patterns of EphA4, ephrin-A2 and ephrin-A5 mRNAs and proteins are highly complex and appear to exhibit some overlap during motor axon outgrowth and pathfinding to the hindlimb, reminiscent of the co-expression of Eph RTKs and ephrins in the retinotectal system. EphA4, similar to the carbohydrate moiety polysialic acid, strikingly marks the main dorsal, but not ventral, nerve trunk after axon sorting at the limb plexus region. Our results suggest that EphA4 RTK and its ligands may influence axon fasciculation and the sorting of axons at the limb plexus, contributing to the correct dorsoventral organization of nerve branches in the hindlimb.
在神经发育过程中，脊髓运动轴突以精确的方式从发育中的脊髓腹侧部分延伸，以支配肢体中的肌肉靶点。尽管在鸟类中的经典研究已经描述了影响运动轴突向肢体寻路的细胞相互作用，但对于介导这一发育事件的分子机制了解较少。在这里，我们研究了EphA4受体酪氨酸激酶（RTK）及其同源配体ephrin-A2和ephrin-A5在运动神经元、它们的轴突以及它们通向鸟类后肢的路径上的时空分布，以确定这些分子是否可能影响轴突投射。EphA4、ephrin-A2和ephrin-A5 mRNA及蛋白质的表达模式高度复杂，并且在运动轴突向肢体生长和寻路过程中似乎存在一些重叠，这让人联想到视网膜顶盖系统中Eph RTK和ephrin的共表达。与碳水化合物部分多唾液酸类似，EphA4在肢体神经丛区域轴突分选后显著标记主要的背侧而非腹侧神经干。我们的结果表明，EphA4 RTK及其配体可能影响轴突成束以及肢体神经丛处轴突的分选，有助于后肢神经分支正确的背腹组织。
