Opposing roles for neurotrophin-3 in targeting and collateral formation of distinct sets of developing cortical neurons.
Opposing roles for neurotrophin-3 in targeting and collateral formation of distinct sets of developing cortical neurons.
复制标题
神经营养素 3 在不同组发育中的皮质神经元的靶向和并行形成中发挥相反的作用。
作者：
V. Castellani;Jürgen Bolz
神经营养素-3及其受体TrkC在哺乳动物大脑皮层发育过程中表达。为了检查神经营养素-3是否可能在层特异性皮层回路的阐述中发挥作用，在外源性应用的神经营养素-3存在下培养层6和层2/3神经元的切片。结果表明，神经营养素-3促进第6层轴突的轴突分支，其靶向体内神经营养素-3表达层，并且其抑制第2/3层轴突的分支，其避免神经营养素-3表达层。神经营养因子-3对轴突分支的这种相反的作用也在胚胎皮层神经元中观察到，表明对神经营养因子-3的反应在细胞迁移之前的早期发育阶段被指定。除了其对纤维分支的影响之外，轴突引导测定还表明，神经营养素-3对于第6层轴突是有吸引力的信号，并且对于第2/3层轴突是排斥性的引导线索。用特异性抗体中和皮质膜中的神经营养素-3的实验揭示，神经营养素-3的内源性水平足以调节皮质轴突的分支和靶向。神经营养素-3对特定轴突群体的这些相反作用表明，它可以作为局部皮层回路的详细说明的信号之一。
Neurotrophin-3 and its receptor TrkC are expressed during the development of the mammalian cerebral cortex. To examine whether neurotrophin-3 might play a role in the elaboration of layer-specific cortical circuits, slices of layer 6 and layers 2/3 neurons were cultured in the presence of exogenously applied neurotrophin-3. Results indicate that neurotrophin-3 promotes axonal branching of layer 6 axons, which target neurotrophin-3-expressing layers in vivo, and that it inhibits branching of layers 2/3 axons, which avoid neurotrophin-3-expressing layers. Such opposing effects of neurotrophin-3 on axonal branching were also observed with embryonic cortical neurons, indicating that the response to neurotrophin-3 is specified at early developmental stages, prior to cell migration. In addition to its effects on fiber branching, axonal guidance assays also indicate that neurotrophin-3 is an attractive signal for layer 6 axons and a repellent guidance cue for layers 2/3 axons. Experiments with specific antibodies to neutralize neurotrophin-3 in cortical membranes revealed that endogenous levels of neurotrophin-3 are sufficient to regulate branching and targeting of cortical axons. These opposing effects of neurotrophin-3 on specific populations of axons demonstrate that it could serve as one of the signals for the elaboration of local cortical circuits.