GAP-43 promoter elements in transgenic zebrafish reveal a difference in signals for axon growth during CNS development and regeneration.
GAP-43 promoter elements in transgenic zebrafish reveal a difference in signals for axon growth during CNS development and regeneration.
复制标题
DOI：
--
复制
发表时间：
2001-04
期刊：
影响因子：
4.6
通讯作者：
A. Udvadia;R. Köster;J. Skene
中科院分区：
文献类型：
--
作者：
A. Udvadia;R. Köster;J. Skene
神经发育中的一个关键事件是分化中的神经元变得有能力延伸长轴突的点。轴突生长的启动对于再生同样至关重要。然而，我们有一个有限的了解信号通路，调节轴突生长的能力，无论是在发展或再生。许多编码生长相关蛋白（GAP）的基因的表达伴随着发育和再生轴突的生长，并导致了相同的信号通路调节两种模式的轴突生长的建议。我们已经测试了这种可能性，询问是否启动子片段从一个良好的特点GAP基因，GAP-43，是足以激活表达在发育和再生神经元。我们产生了稳定的转基因斑马鱼线，表达绿色荧光蛋白（GFP）的大鼠GAP-43基因的1 kb片段的调控下，一个片段，包含了一些进化保守的元素。在这些线中的GFP表达的分析证实，大鼠1 kb区域可以直接生长相关的表达的转基因在分化的神经元，延长长轴突。此外，该区域支持转基因表达的发育下调，这与内源性基因一样，与神经元成熟一致。引人注目的是，这些相同的序列不足以指导再生神经元的表达。这一发现表明，在发育和再生过程中调节轴突生长的信号通路是不同的。虽然这些结果并不排除参与发育轴突生长的途径在再生生长中也是活跃的可能性，但它们确实表明CNS损伤后控制差距-43基因活化的信号传导途径在至少一个关键组分上与控制发育轴突生长的基本特征的信号不同。
A pivotal event in neural development is the point at which differentiating neurons become competent to extend long axons. Initiation of axon growth is equally critical for regeneration. Yet we have a limited understanding of the signaling pathways that regulate the capacity for axon growth during either development or regeneration. Expression of a number of genes encoding growth associated proteins (GAPs) accompanies both developmental and regenerative axon growth and has led to the suggestion that the same signaling pathways regulate both modes of axon growth. We have tested this possibility by asking whether a promoter fragment from a well characterized GAP gene, GAP-43, is sufficient to activate expression in both developing and regenerating neurons. We generated stable lines of transgenic zebrafish that express green fluorescent protein (GFP) under regulation of a 1 kb fragment of the rat GAP-43 gene, a fragment that contains a number of evolutionarily conserved elements. Analysis of GFP expression in these lines confirms that the rat 1 kb region can direct growth-associated expression of the transgene in differentiating neurons that extend long axons. Furthermore, this region supports developmental down-regulation of transgene expression which, like the endogenous gene, coincides with neuronal maturation. Strikingly, these same sequences are insufficient for directing expression in regenerating neurons. This finding suggests that signaling pathways regulating axon growth during development and regeneration are not the same. While these results do not exclude the possibility that pathways involved in developmental axon growth are also active in regenerative growth, they do indicate that signaling pathway(s) controlling activation of the GAP-43 gene after CNS injury differ in at least one key component from the signals controlling essential features of developmental axon growth.