cJun promotes CNS axon growth.

cJun promotes CNS axon growth.
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DOI:
10.1016/j.mcn.2014.02.002
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发表时间:
2014-03
期刊:
Molecular and cellular neurosciences
影响因子:
--
通讯作者:
Lemmon VP
Lemmon VP
中科院分区:
其他
文献类型:
--
作者:
Lerch JK;Martínez-Ondaro YR;Bixby JL;Lemmon VP

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许多基因调节外周轴突的再生,但它们在中枢神经系统(CNS)中驱动轴突生长和再生的能力在很大程度上仍未得到测试。为了解决这个问题,我们单独和成对组合过表达了八个转录因子和一个小的GTP酶,以测试组合过表达是否会对中枢神经系统神经元突起的生长产生协同影响。Jun癌基因/信号转导和转录激活因子6(Jun/STAT6)组合可促进分离的皮质神经元和损伤皮质脑片中的轴突生长。在损伤的皮质切片中,Jun过表达促进轴突生长的程度与Jun和STAT6共同作用的程度相似。有趣的是,Jun的过度表达与生长相关蛋白43(GAP43)或整合素α7(ITGA7)的表达增加无关,尽管这些都是预测的转录目标。这项研究表明,Jun在皮质神经元中的过度表达可以刺激轴突生长,但这种作用不依赖于被认为对Jun影响轴突生长至关重要的基因表达的变化。我们得出结论,Jun活性是这种中枢神经系统轴突生长反应的基础,它与外周再生反应在机械上是不同的,在外周再生反应中,Jun表达的增加与GAP43的表达增加是一致的。
A number of genes regulate regeneration of peripheral axons, but their ability to drive axon growth and regeneration in the central nervous system (CNS) remains largely untested. To address this question we overexpressed eight transcription factors and one small GTPase alone and in pairwise combinations to test whether combinatorial overexpression would have a synergistic impact on CNS neuron neurite growth. The Jun oncogene/signal transducer and activator of transcription 6 (JUN/STAT6) combination increased neurite growth in dissociated cortical neurons and in injured cortical slices. In injured cortical slices, JUN overexpression increased axon growth to a similar extent as JUN and STAT6 together. Interestingly, JUN overexpression was not associated with increased growth associated protein 43 (GAP43) or integrin alpha 7 (ITGA7) expression, though these are predicted transcriptional targets. This study demonstrates that JUN overexpression in cortical neurons stimulates axon growth, but does so independently of changes in expression of genes thought to be critical for JUN’s effects on axon growth. We conclude that JUN activity underlies this CNS axonal growth response, and that it is mechanistically distinct from peripheral regeneration responses, in which increases in JUN expression coincide with increases in GAP43 expression.
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