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1.
J Cell Biochem ; 117(8): 1880-9, 2016 08.
Article in English | MEDLINE | ID: mdl-26755079

ABSTRACT

In vertebrates, damage to mechanosensory hair cells elicits an inflammatory response, including rapid recruitment of macrophages and neutrophils. While hair cells in amniotes usually become permanently lost, they readily regenerate in lower vertebrates such as fish. Damage to hair cells of the fish lateral line is followed by inflammation and rapid regeneration; however the role of immune cells in this process remains unknown. Here, we show that recruited macrophages are required for normal regeneration of lateral line hair cells after copper damage. We found that genetic ablation or local ablation using clodronate liposomes of macrophages recruited to the site of injury, significantly delays hair cell regeneration. Neutrophils, on the other hand, are not needed for this process. We anticipate our results to be a starting point for a more detailed description of extrinsic signals important for regeneration of mechanosensory cells in vertebrates. J. Cell. Biochem. 117: 1880-1889, 2016. © 2016 Wiley Periodicals, Inc.


Subject(s)
Animal Structures/physiology , Copper/toxicity , Macrophages/immunology , Mechanotransduction, Cellular/immunology , Neurons, Afferent/immunology , Regeneration/immunology , Zebrafish/immunology , Animals , Neutrophils/immunology
2.
Neural Dev ; 7: 19, 2012 Jun 08.
Article in English | MEDLINE | ID: mdl-22681863

ABSTRACT

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.


Subject(s)
Axons/physiology , Gene Expression Regulation, Developmental/physiology , Nerve Degeneration/physiopathology , Nerve Regeneration/physiology , Neurons/cytology , Peripheral Nerves/cytology , Analysis of Variance , Animals , Animals, Genetically Modified , Axotomy , Copper/pharmacology , Copper/therapeutic use , Embryo, Nonmammalian , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Gene Expression Regulation, Developmental/drug effects , Gene Expression Regulation, Developmental/genetics , Green Fluorescent Proteins/genetics , Mutation/genetics , Nerve Degeneration/drug therapy , Nerve Degeneration/metabolism , Nerve Degeneration/pathology , Nerve Regeneration/drug effects , Nerve Regeneration/genetics , Oligodeoxyribonucleotides, Antisense/pharmacology , Peripheral Nerves/embryology , Proto-Oncogene Proteins/genetics , Quinazolines/pharmacology , Quinazolines/therapeutic use , Schwann Cells/cytology , Schwann Cells/drug effects , Trans-Activators/genetics , Transcription Factors/genetics , Tyrphostins/pharmacology , Tyrphostins/therapeutic use , Zebrafish , Zebrafish Proteins/genetics
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