Metamorphosis and the regenerative capacity of spinal cord axons in Xenopus laevis
Metamorphosis and the regenerative capacity of spinal cord axons in Xenopus laevis
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DOI：
10.1111/j.1460-9568.2010.07477.x
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发表时间：
2011-01-01
影响因子：
3.4
通讯作者：
Szaro, Ben G.
中科院分区：
文献类型：
--
作者：
Gibbs, Kurt M.;Chittur, Sridar V.;Szaro, Ben G.
在整个脊椎动物亚门中，中枢神经系统轴突的再生潜力在胚胎期最大，并随着发育的进展而下降。例如，非洲爪哇可以像蝌蚪一样从脊髓完全横断中恢复功能，但在蜕变成青蛙后就无法恢复。在蝌蚪中，网状结构和中缝核神经元是再生轴突最可靠的神经元之一，在变形后失去这种能力。为了确定与脊髓轴突再生成功和失败相关的分子因素，我们使用他巴唑或三碘甲腺原氨酸对甲状腺激素(TH)水平进行了药理操作，分别使蝌蚪处于永久幼虫状态或诱导性早熟变态。脊髓全横断后，5-羟色胺能轴突穿过损伤部位，变形被抑制后，蝌蚪游泳能力恢复，但在过早诱导变形时，这些事件未能发生。因此，受TH控制的变质事件直接导致再生势的丧失。微阵列分析确定了伴随着再生允许和抑制条件的后脑基因表达的变化，包括许多以前与轴突生长和神经保护相关的基因。这些数据表明，在再生允许的条件下，在正常发育暂停的情况下，再生神经元内的基因表达发生了变化，并为未来研究一些脊椎动物的中枢神经系统轴突如何成功再生确定了候选基因。
Throughout the vertebrate subphylum, the regenerative potential of central nervous system axons is greatest in embryonic stages and declines as development progresses. For example, Xenopus laevis can functionally recover from complete transection of the spinal cord as a tadpole but is unable to do so after metamorphosing into a frog. Neurons of the reticular formation and raphe nucleus are among those that regenerate axons most reliably in tadpole and that lose this ability after metamorphosis. To identify molecular factors associated with the success and failure of spinal cord axon regeneration, we pharmacologically manipulated thyroid hormone (TH) levels using methimazole or triiodothyronine, to either keep tadpoles in a permanently larval state or induce precocious metamorphosis, respectively. Following complete spinal cord transection, serotonergic axons crossed the lesion site and tadpole swimming ability was restored when metamorphosis was inhibited, but these events failed to occur when metamorphosis was prematurely induced. Thus, the metamorphic events controlled by TH led directly to the loss of regenerative potential. Microarray analysis identified changes in hindbrain gene expression that accompanied regeneration-permissive and -inhibitory conditions, including many genes in the permissive condition that have been previously associated with axon outgrowth and neuroprotection. These data demonstrate that changes in gene expression occur within regenerating neurons in response to axotomy under regeneration-permissive conditions in which normal development has been suspended, and they identify candidate genes for future studies of how central nervous system axons can successfully regenerate in some vertebrates.