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Proliferative regeneration of zebrafish lateral line hair cells after different ototoxic insults.

Mackenzie SM, Raible DW - PLoS ONE (2012)

Bottom Line: Certain treatments, including cisplatin and higher concentrations of dissolved copper, significantly delayed regeneration by one or more days.However, cisplatin did not block all regeneration as observed previously in the chick basilar papilla.The particular ototoxin did not appear to affect the mechanism of regeneration, as we observed evidence of recent proliferation in the majority of new hair cells in all cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
Sensory hair cells in the zebrafish lateral line regenerate rapidly and completely after damage. Previous studies have used a variety of ototoxins to kill lateral line hair cells to study different phenomena including mechanisms of hair cell death and regeneration. We sought to directly compare these ototoxins to determine if they differentially affected the rate and amount of hair cell replacement. In addition, previous studies have found evidence of proliferative hair cell regeneration in zebrafish, but both proliferation and non-mitotic direct transdifferentiation have been observed during hair cell regeneration in the sensory epithelia of birds and amphibians. We sought to test whether a similar combination of regenerative mechanisms exist in the fish. We analyzed the time course of regeneration after treatment with different ototoxic compounds and also labeled dividing hair cell progenitors. Certain treatments, including cisplatin and higher concentrations of dissolved copper, significantly delayed regeneration by one or more days. However, cisplatin did not block all regeneration as observed previously in the chick basilar papilla. The particular ototoxin did not appear to affect the mechanism of regeneration, as we observed evidence of recent proliferation in the majority of new hair cells in all cases. Inhibiting proliferation with flubendazole blocked the production of new hair cells and prevented the accumulation of additional precursors, indicating that proliferation has a dominant role during regeneration of lateral line hair cells.

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Rapid hair cell loss after treatment with water-borne copper.Wild type larvae were treated at 5 dpf with serial dilutions of copper(II) sulfate for a period of 30 min to 8 h. Hair cell death was rapid in most cases, although 0.3 μM copper had a minimal effect. N = 8 fish per group. Error bars are +/− SD.
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pone-0047257-g001: Rapid hair cell loss after treatment with water-borne copper.Wild type larvae were treated at 5 dpf with serial dilutions of copper(II) sulfate for a period of 30 min to 8 h. Hair cell death was rapid in most cases, although 0.3 μM copper had a minimal effect. N = 8 fish per group. Error bars are +/− SD.

Mentions: We have previously shown that media composition alters hair cell toxicity [48]. To ensure copper treatments effectively killed hair cells under conditions comparable to those used with aminoglycoside antibiotics, we performed a dose response assay using 5 dpf wild type *AB larvae treated with concentrations of dissolved copper(II) sulfate ranging from 0.3–30 μM and continuous exposure times ranging from 30 min to 10 h. These data show a consistent relationship between concentration, duration of exposure, and hair cell death (Figure 1) that is similar to previous reports [17], [36]. While 1 μM copper killed nearly all hair cells within 4 h, higher concentrations were effective within 30–60 min. The interplay between concentration and time of treatment suggests that copper may act in a cumulative fashion to damage hair cells.


Proliferative regeneration of zebrafish lateral line hair cells after different ototoxic insults.

Mackenzie SM, Raible DW - PLoS ONE (2012)

Rapid hair cell loss after treatment with water-borne copper.Wild type larvae were treated at 5 dpf with serial dilutions of copper(II) sulfate for a period of 30 min to 8 h. Hair cell death was rapid in most cases, although 0.3 μM copper had a minimal effect. N = 8 fish per group. Error bars are +/− SD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475690&req=5

pone-0047257-g001: Rapid hair cell loss after treatment with water-borne copper.Wild type larvae were treated at 5 dpf with serial dilutions of copper(II) sulfate for a period of 30 min to 8 h. Hair cell death was rapid in most cases, although 0.3 μM copper had a minimal effect. N = 8 fish per group. Error bars are +/− SD.
Mentions: We have previously shown that media composition alters hair cell toxicity [48]. To ensure copper treatments effectively killed hair cells under conditions comparable to those used with aminoglycoside antibiotics, we performed a dose response assay using 5 dpf wild type *AB larvae treated with concentrations of dissolved copper(II) sulfate ranging from 0.3–30 μM and continuous exposure times ranging from 30 min to 10 h. These data show a consistent relationship between concentration, duration of exposure, and hair cell death (Figure 1) that is similar to previous reports [17], [36]. While 1 μM copper killed nearly all hair cells within 4 h, higher concentrations were effective within 30–60 min. The interplay between concentration and time of treatment suggests that copper may act in a cumulative fashion to damage hair cells.

Bottom Line: Certain treatments, including cisplatin and higher concentrations of dissolved copper, significantly delayed regeneration by one or more days.However, cisplatin did not block all regeneration as observed previously in the chick basilar papilla.The particular ototoxin did not appear to affect the mechanism of regeneration, as we observed evidence of recent proliferation in the majority of new hair cells in all cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Structure, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
Sensory hair cells in the zebrafish lateral line regenerate rapidly and completely after damage. Previous studies have used a variety of ototoxins to kill lateral line hair cells to study different phenomena including mechanisms of hair cell death and regeneration. We sought to directly compare these ototoxins to determine if they differentially affected the rate and amount of hair cell replacement. In addition, previous studies have found evidence of proliferative hair cell regeneration in zebrafish, but both proliferation and non-mitotic direct transdifferentiation have been observed during hair cell regeneration in the sensory epithelia of birds and amphibians. We sought to test whether a similar combination of regenerative mechanisms exist in the fish. We analyzed the time course of regeneration after treatment with different ototoxic compounds and also labeled dividing hair cell progenitors. Certain treatments, including cisplatin and higher concentrations of dissolved copper, significantly delayed regeneration by one or more days. However, cisplatin did not block all regeneration as observed previously in the chick basilar papilla. The particular ototoxin did not appear to affect the mechanism of regeneration, as we observed evidence of recent proliferation in the majority of new hair cells in all cases. Inhibiting proliferation with flubendazole blocked the production of new hair cells and prevented the accumulation of additional precursors, indicating that proliferation has a dominant role during regeneration of lateral line hair cells.

Show MeSH
Related in: MedlinePlus