Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 23, Pages 6010-6021Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0101-08.2008
Keywords
Drosophila; explant; injury; regeneration; signal transduction
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Funding
- Direct For Biological Sciences [0757242] Funding Source: National Science Foundation
- Division Of Integrative Organismal Systems [0757242] Funding Source: National Science Foundation
- NINDS NIH HHS [R01 NS046750-02, R01 NS046750-04, R01-NS046750, R01 NS046750-03, R01 NS046750, R01 NS046750-01A1] Funding Source: Medline
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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.
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