Journal
NEURAL DEVELOPMENT
Volume 7, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1749-8104-7-19
Keywords
In vivo axotomy; Wallerian degeneration; Schwann cells; Leukocytes; Hair cells; Neurons; Lateral line
Categories
Funding
- CONICYT [21060426, 24080075, 23110054]
- MECESUP
- Company of Biologists, IBRO, Boehringher Ingelheim Fonds
- Vicerrectoria de Asuntos Academicos, Universidad de Chile
- National Institute of Dental and Craniofacial Research (NIDCR)
- UCLA Training Program in Neural Repair
- National Institute of Neurological Disorders [NINDS 5/T32/NS07449:13]
- FONDAP [15090007]
- FONDECYT [1110275]
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Background: Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function. Many studies of axonal degeneration and regeneration have used in vitro approaches, but the influence of extrinsic cell types on these processes can only be fully addressed in live animals. Because of its simplicity and superficial location, the larval zebrafish posterior lateral line (pLL) nerve is an ideal model system for live studies of axon degeneration and regeneration. Results: We used laser axotomy and time-lapse imaging of pLL axons to characterize the roles of leukocytes, Schwann cells and target sensory hair cells in axon degeneration and regeneration in vivo. Immune cells were essential for efficient removal of axonal debris after axotomy. Schwann cells were required for proper fasciculation and pathfinding of regenerating axons to their target cells. Intact target hair cells were not themselves required for regeneration, but chemical ablation of neuromasts caused axons to transiently deviate from their normal paths. Conclusions: Macrophages, Schwann cells, and target sensory organs are required for distinct aspects of pLL axon degeneration or regeneration in the zebrafish larva. Our work introduces a powerful vertebrate model for analyzing axonal degeneration and regeneration in the living animal and elucidating the role of extrinsic cell types in these processes.
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