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Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin.

Rieger S, Sagasti A - PLoS Biol. (2011)

Bottom Line: To investigate how sensory axon regeneration and wound healing are coordinated, we amputated the caudal fins of zebrafish larvae and imaged somatosensory axon behavior.Exposure of zebrafish larvae to sublethal levels of exogenous H(2)O(2) promoted growth of severed axons in the absence of keratinocyte injury, and inhibiting H(2)O(2) production blocked the axon growth-promoting effects of fin amputation and keratinocyte ablation.Thus, H(2)O(2) signaling helps coordinate wound healing with peripheral sensory axon reinnervation of the skin.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, University of California Los Angeles, Los Angeles, California, United States of America. srieger@mcdb.ucla.edu

ABSTRACT
Functional recovery from cutaneous injury requires not only the healing and regeneration of skin cells but also reinnervation of the skin by somatosensory peripheral axon endings. To investigate how sensory axon regeneration and wound healing are coordinated, we amputated the caudal fins of zebrafish larvae and imaged somatosensory axon behavior. Fin amputation strongly promoted the regeneration of nearby sensory axons, an effect that could be mimicked by ablating a few keratinocytes anywhere in the body. Since injury produces the reactive oxygen species hydrogen peroxide (H(2)O(2)) near wounds, we tested whether H(2)O(2) influences cutaneous axon regeneration. Exposure of zebrafish larvae to sublethal levels of exogenous H(2)O(2) promoted growth of severed axons in the absence of keratinocyte injury, and inhibiting H(2)O(2) production blocked the axon growth-promoting effects of fin amputation and keratinocyte ablation. Thus, H(2)O(2) signaling helps coordinate wound healing with peripheral sensory axon reinnervation of the skin.

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Sensory axons innervate regenerated fins.(A) Quantification of the density of axons within regenerated fins as measured by pixel density in a 50 µm2 area (white box) at the distal fin tip. No significant difference was found between groups (one-way ANOVA and Bonferroni's post-test for comparison of all groups was applied; p = ns>0.05). (B) Reinnervating sensory axons are functional. Uninjured larvae at 6 dpf were compared to amputated larvae at 3 dpa (6 dpf) in their ability to escape in response to touch stimuli at the caudal fin tip (11/12 uninjured fish escaped, 13/14 injured/regenerated fish escaped).
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pbio-1000621-g002: Sensory axons innervate regenerated fins.(A) Quantification of the density of axons within regenerated fins as measured by pixel density in a 50 µm2 area (white box) at the distal fin tip. No significant difference was found between groups (one-way ANOVA and Bonferroni's post-test for comparison of all groups was applied; p = ns>0.05). (B) Reinnervating sensory axons are functional. Uninjured larvae at 6 dpf were compared to amputated larvae at 3 dpa (6 dpf) in their ability to escape in response to touch stimuli at the caudal fin tip (11/12 uninjured fish escaped, 13/14 injured/regenerated fish escaped).

Mentions: The caudal fins of larval zebrafish regenerate completely within a few days after amputation [20], implying that RB peripheral axons must also regenerate to provide sensory function to the new fin. To directly assess whether RB axons in the tail can regenerate, we imaged GFP-labeled RB arbors in the islet2b:GFP transgenic line [25] after caudal fin amputation at 3 d post-fertilization (dpf). Amputation caused immediate degeneration of axon branches near the wound (Figure 1B, brackets), creating a denervated zone that regenerating axons would need to traverse to fully innervate the regenerating fin. Despite this potential barrier, the fin was always reinnervated by RB arbors at 120 h post-amputation (hpamp) (Figure 1B). Three days after fin amputation, there was no detectable difference in the total amount of sensory axons in regenerated fin tips and fin tips of age-matched animals (6 dpf) that were never injured, indicating that reinnervation of regenerated fins was complete (Figure 2A). Sensory reinnervation of regenerated fins was functional, since 6 dpf fish with regenerated fins responded to touch at the tip of the tail as often as uninjured control fish (Figure 2B).


Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin.

Rieger S, Sagasti A - PLoS Biol. (2011)

Sensory axons innervate regenerated fins.(A) Quantification of the density of axons within regenerated fins as measured by pixel density in a 50 µm2 area (white box) at the distal fin tip. No significant difference was found between groups (one-way ANOVA and Bonferroni's post-test for comparison of all groups was applied; p = ns>0.05). (B) Reinnervating sensory axons are functional. Uninjured larvae at 6 dpf were compared to amputated larvae at 3 dpa (6 dpf) in their ability to escape in response to touch stimuli at the caudal fin tip (11/12 uninjured fish escaped, 13/14 injured/regenerated fish escaped).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3101194&req=5

pbio-1000621-g002: Sensory axons innervate regenerated fins.(A) Quantification of the density of axons within regenerated fins as measured by pixel density in a 50 µm2 area (white box) at the distal fin tip. No significant difference was found between groups (one-way ANOVA and Bonferroni's post-test for comparison of all groups was applied; p = ns>0.05). (B) Reinnervating sensory axons are functional. Uninjured larvae at 6 dpf were compared to amputated larvae at 3 dpa (6 dpf) in their ability to escape in response to touch stimuli at the caudal fin tip (11/12 uninjured fish escaped, 13/14 injured/regenerated fish escaped).
Mentions: The caudal fins of larval zebrafish regenerate completely within a few days after amputation [20], implying that RB peripheral axons must also regenerate to provide sensory function to the new fin. To directly assess whether RB axons in the tail can regenerate, we imaged GFP-labeled RB arbors in the islet2b:GFP transgenic line [25] after caudal fin amputation at 3 d post-fertilization (dpf). Amputation caused immediate degeneration of axon branches near the wound (Figure 1B, brackets), creating a denervated zone that regenerating axons would need to traverse to fully innervate the regenerating fin. Despite this potential barrier, the fin was always reinnervated by RB arbors at 120 h post-amputation (hpamp) (Figure 1B). Three days after fin amputation, there was no detectable difference in the total amount of sensory axons in regenerated fin tips and fin tips of age-matched animals (6 dpf) that were never injured, indicating that reinnervation of regenerated fins was complete (Figure 2A). Sensory reinnervation of regenerated fins was functional, since 6 dpf fish with regenerated fins responded to touch at the tip of the tail as often as uninjured control fish (Figure 2B).

Bottom Line: To investigate how sensory axon regeneration and wound healing are coordinated, we amputated the caudal fins of zebrafish larvae and imaged somatosensory axon behavior.Exposure of zebrafish larvae to sublethal levels of exogenous H(2)O(2) promoted growth of severed axons in the absence of keratinocyte injury, and inhibiting H(2)O(2) production blocked the axon growth-promoting effects of fin amputation and keratinocyte ablation.Thus, H(2)O(2) signaling helps coordinate wound healing with peripheral sensory axon reinnervation of the skin.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, University of California Los Angeles, Los Angeles, California, United States of America. srieger@mcdb.ucla.edu

ABSTRACT
Functional recovery from cutaneous injury requires not only the healing and regeneration of skin cells but also reinnervation of the skin by somatosensory peripheral axon endings. To investigate how sensory axon regeneration and wound healing are coordinated, we amputated the caudal fins of zebrafish larvae and imaged somatosensory axon behavior. Fin amputation strongly promoted the regeneration of nearby sensory axons, an effect that could be mimicked by ablating a few keratinocytes anywhere in the body. Since injury produces the reactive oxygen species hydrogen peroxide (H(2)O(2)) near wounds, we tested whether H(2)O(2) influences cutaneous axon regeneration. Exposure of zebrafish larvae to sublethal levels of exogenous H(2)O(2) promoted growth of severed axons in the absence of keratinocyte injury, and inhibiting H(2)O(2) production blocked the axon growth-promoting effects of fin amputation and keratinocyte ablation. Thus, H(2)O(2) signaling helps coordinate wound healing with peripheral sensory axon reinnervation of the skin.

Show MeSH
Related in: MedlinePlus