Axonal injury and regeneration in the adult brain of Drosophila

被引:73
作者
Ayaz, Derya [1 ,2 ,3 ]
Leyssen, Maarten [1 ,2 ]
Koch, Marta [1 ,2 ]
Yan, Jiekun [1 ,2 ]
Srahna, Mohammed [1 ,2 ]
Sheeba, Vasu [5 ]
Fogle, Keri J. [5 ]
Holmes, Todd C. [2 ,5 ]
Hassan, Bassem A. [1 ,2 ,3 ,4 ]
机构
[1] Flanders Inst Biotechnol VIB, Dept Mol & Dev Genet, Lab Neurogenet, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Sch Med, Dept Human Genet, B-3000 Louvain, Belgium
[3] Katholieke Univ Leuven, Grp Biomed, Program Mol & Dev Genet, B-3000 Louvain, Belgium
[4] Katholieke Univ Leuven, Grp Biomed, Program Mol & Cognit Neurosci, B-3000 Louvain, Belgium
[5] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA
基金
美国国家科学基金会;
关键词
Drosophila; explant; injury; regeneration; signal transduction;
D O I
10.1523/JNEUROSCI.0101-08.2008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:6010 / 6021
页数:12
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