Ebens A, Brose K, Leonardo E D, Hanson M G, Bladt F, Birchmeier C, Barres B A, Tessier-Lavigne M
Howard Hughes Medical Institute, Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Neuron. 1996 Dec;17(6):1157-72. doi: 10.1016/s0896-6273(00)80247-0.
In the embryonic nervous system, developing axons can be guided to their targets by diffusible factors secreted by their intermediate and final cellular targets. To date only one family of chemoattractants for developing axons has been identified. Grafting and ablation experiments in fish, amphibians, and birds have suggested that spinal motor axons are guided to their targets in the limb in part by a succession of chemoattractants made by the sclerotome and by the limb mesenchyme, two intermediate targets that these axons encounter en route to their target muscles. Here we identify the limb mesenchyme-derived chemoattractant as hepatocyte growth factor/scatter factor (HGF/SF), a diffusible ligand for the c-Met receptor tyrosine kinase, and we also implicate HGF/SF at later stages as a muscle-derived survival factor for motoneurons. These results indicate that, in addition to functioning as a mitogen, a motogen, and a morphogen in nonneural systems, HGF/SF can function as a guidance and survival factor in the developing nervous system.
在胚胎神经系统中,发育中的轴突可被其中间和最终细胞靶点分泌的可扩散因子引导至其靶点。迄今为止,仅鉴定出一个用于发育中轴突的趋化因子家族。在鱼类、两栖类和鸟类中进行的移植和消融实验表明,脊髓运动轴突在肢体中被引导至其靶点,部分是通过由硬骨节和肢体间充质产生的一系列趋化因子,这两个中间靶点是这些轴突在通往其靶肌肉的途中遇到的。在这里,我们确定肢体间充质来源的趋化因子为肝细胞生长因子/分散因子(HGF/SF),它是c-Met受体酪氨酸激酶的一种可扩散配体,并且我们还表明HGF/SF在后期作为运动神经元的肌肉来源存活因子发挥作用。这些结果表明,除了在非神经系统中作为有丝分裂原、促有丝分裂原和形态发生原发挥作用外,HGF/SF在发育中的神经系统中还可作为引导和存活因子发挥作用。