Cohen-Cory S, Fraser S E
Division of Biology, 139-74, California Institute of Technology, Pasadena 91125, USA.
Nature. 1995 Nov 9;378(6553):192-6. doi: 10.1038/378192a0.
Neurotrophins are thought to be important for the survival and differentiation of vertebrate neurons. Roles have been suggested for target-derived neurotrophins, based both on their expression in target tissues at the time of neuron innervation, and on their effects on axonal sprouting. However, direct in vivo evidence of their involvement in axon arborization has remained elusive. We have used in vivo microscopy to follow individual optic axons over time, and have examined the role of the neurotrophin brain-derived neurotrophic factor (BDNF) in their development. Here we show that injection of BDNF into the optic tectum of live Xenopus laevis tadpoles increased the branching and complexity of optic axon terminal arbors. In contrast, injection of specific neutralizing antibodies to BDNF reduced axon arborization and complexity. The onset of these effects was rapid (within 2 hours) and persisted throughout the 24-hour observation period. Other neurotrophins had little or no significant effects. These results demonstrate the involvement of neurotrophins in the dynamic elaboration of axon terminals, and suggest a direct role for target-derived BDNF during synaptic patterning in the developing central nervous system.
神经营养因子被认为对脊椎动物神经元的存活和分化至关重要。基于神经营养因子在神经元支配时在靶组织中的表达以及它们对轴突发芽的影响，有人提出了靶源性神经营养因子的作用。然而，它们参与轴突分支的直接体内证据仍然难以捉摸。我们利用体内显微镜技术随时间追踪单个视神经轴突，并研究了神经营养因子脑源性神经营养因子（BDNF）在其发育过程中的作用。在此我们表明，将BDNF注入活的非洲爪蟾蝌蚪的视顶盖会增加视神经轴突终末分支的分支数量和复杂性。相反，注射针对BDNF的特异性中和抗体则会减少轴突分支和复杂性。这些效应的起始迅速（在2小时内），并在整个24小时观察期内持续存在。其他神经营养因子几乎没有显著影响。这些结果证明了神经营养因子参与轴突终末的动态细化，并表明靶源性BDNF在发育中的中枢神经系统突触形成过程中具有直接作用。
