Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types

• Published in: Neural development Vol. 7; no. 1; p. 19
• Main Authors: Villegas, Rosario, Martin, Seanna M, O'Donnell, Kelley C, Carrillo, Simon A, Sagasti, Alvaro, Allende, Miguel L
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.06.2012; BioMed Central; BMC
• Subjects: Analysis of Variance; Animals; Animals, Genetically Modified; Axons - physiology; Axotomy; Copper - pharmacology; Copper - therapeutic use; Danio rerio; Embryo, Nonmammalian; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Experiments; Freshwater; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - genetics; Gene Expression Regulation, Developmental - physiology; Green Fluorescent Proteins - genetics; Hair; Hair cells; In vivo axotomy; Lateral line; Leukocytes; Metabolic disorders; Mutation - genetics; Nerve Degeneration - drug therapy; Nerve Degeneration - metabolism; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Nerve Regeneration - drug effects; Nerve Regeneration - genetics; Nerve Regeneration - physiology; Nervous system; Nervous system diseases; Neurons; Neurons - cytology; Oligodeoxyribonucleotides, Antisense - pharmacology; Peripheral Nerves - cytology; Peripheral Nerves - embryology; Physiological aspects; Proteins; Proto-Oncogene Proteins - genetics; Quinazolines - pharmacology; Quinazolines - therapeutic use; Schwann cells; Schwann Cells - cytology; Schwann Cells - drug effects; Trans-Activators - genetics; Transcription Factors - genetics; Tyrphostins - pharmacology; Tyrphostins - therapeutic use; Wallerian degeneration; Zebrafish; Zebrafish Proteins - genetics
• ISSN: 1749-8104; 1749-8104
• DOI: 10.1186/1749-8104-7-19

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. 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. 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.