Axonal injury and regeneration in the adult brain of Drosophila
Axonal injury and regeneration in the adult brain of Drosophila
复制标题
DOI：
10.1523/jneurosci.0101-08.2008
复制
发表时间：
2008-06-04
影响因子：
5.3
通讯作者：
Hassan, Bassem A.
中科院分区：
文献类型：
--
作者：
Ayaz, Derya;Leyssen, Maarten;Hassan, Bassem A.
黑腹果蝇是神经系统发育和疾病研究的主要遗传模式系统。利用果蝇遗传学的力量进行创伤性轴突损伤研究将显著加快控制中枢神经系统轴突再生的分子过程的表征。我们为整个果蝇大脑的长期培养开发了一种多功能和生理上健壮的准备。我们利用这种方法建立了一种新的果蝇中枢神经系统轴突损伤和再生模型。我们首先表明，与哺乳动物中枢神经系统轴突类似，受伤的成年野生型苍蝇中枢神经系统轴突不能再生，而成年特异性增强的蛋白激酶A活性增加了受损神经元的再生能力。综上所述，这些观察结果提示损伤后神经元再生机制的保存。接下来，我们利用该模型探索诱导强大再生的途径，并发现c-Jun n端蛋白激酶信号的成人特异性激活足以引起新生中枢神经系统轴突再生损伤，包括新轴突的生长经过病变部位并进入正常靶区。
Drosophila melanogaster is a leading genetic model system in nervous system development and disease research. Using the power of fly genetics in traumatic axonal injury research will significantly speed up the characterization of molecular processes that control axonal regeneration in the CNS. We developed a versatile and physiologically robust preparation for the long-term culture of the whole Drosophila brain. We use this method to develop a novel Drosophila model for CNS axonal injury and regeneration. We first show that, similar to mammalian CNS axons, injured adult wild-type fly CNS axons fail to regenerate, whereas adult-specific enhancement of protein kinase A activity increases the regenerative capacity of lesioned neurons. Combined, these observations suggest conservation of neuronal regeneration mechanisms after injury. We next exploit this model to explore pathways that induce robust regeneration and find that adult-specific activation of c-Jun N-terminal protein kinase signaling is sufficient for de novo CNS axonal regeneration injury, including the growth of new axons past the lesion site and into the normal target area.