Ayaz Derya, Leyssen Maarten, Koch Marta, Yan Jiekun, Srahna Mohammed, Sheeba Vasu, Fogle Keri J, Holmes Todd C, Hassan Bassem A
Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, Flanders Institute for Biotechnology (VIB), 3000 Leuven, Belgium.
J Neurosci. 2008 Jun 4;28(23):6010-21. doi: 10.1523/JNEUROSCI.0101-08.2008.
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.
黑腹果蝇是神经系统发育和疾病研究中一种重要的遗传模型系统。利用果蝇遗传学在创伤性轴突损伤研究中的优势，将显著加快对中枢神经系统中控制轴突再生的分子过程的表征。我们开发了一种用于长期培养整个果蝇大脑的通用且生理功能强大的制剂。我们使用这种方法建立了一种新型的中枢神经系统轴突损伤和再生的果蝇模型。我们首先表明，与哺乳动物中枢神经系统轴突类似，受伤的成年野生型果蝇中枢神经系统轴突无法再生，而成年期特异性增强蛋白激酶A的活性可增加受损神经元的再生能力。综合这些观察结果表明，损伤后神经元再生机制具有保守性。接下来，我们利用这个模型探索诱导强大再生的途径，发现成年期特异性激活c-Jun氨基末端蛋白激酶信号足以实现中枢神经系统轴突损伤后的从头再生，包括新轴突越过损伤部位并生长到正常靶区域。
