Proliferative Regeneration of Zebrafish Lateral Line Hair Cells after Different Ototoxic Insults 英文参考文献.docVIP

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Proliferative Regeneration of Zebrafish Lateral Line Hair Cells after Different Ototoxic Insults 英文参考文献.doc

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Proliferative Regeneration of Zebrafish Lateral Line Hair Cells after Different Ototoxic Insults 英文参考文献

ProliferativeRegenerationofZebrafishLateralLineHair CellsafterDifferentOtotoxicInsults ScottM.Mackenzie1,2,DavidW.Raible1,2 * 1Department of Biological Structure, University of Washington, Seattle, Washington, United States of America, 2Graduate Program in Neurobiology and Behavior, UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica Abstract Sensoryhaircellsinthezebrafishlaterallineregeneraterapidlyandcompletelyafterdamage.Previousstudieshaveused avarietyofototoxinstokilllaterallinehaircellstostudydifferentphenomenaincludingmechanismsofhaircelldeathand regeneration. We sought to directly compare these ototoxins to determine if they differentially affected the rate and amountofhaircellreplacement.Inaddition,previousstudieshavefoundevidenceofproliferativehaircellregenerationin 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 blockallregenerationasobservedpreviouslyinthechickbasilarpapilla.Theparticularototoxindidnotappeartoaffectthe mechanismofregeneration,asweobservedevidenceofrecentproliferationinthemajorityofnewhaircellsinallcases. Inhibiting proliferation with flubendazole blocked the production of new hair cells and prevented the accumulation of additionalprecursors,indicatingthatproliferationhasadominantroleduringregenerationoflaterallinehaircells. Citation:MackenzieSM,RaibleDW(2012)ProliferativeRegenerationofZebrafishLateralLineHairCellsafterDifferentOtotoxicInsults.PLoSONE7(10):e47257. doi:10.1371/journal.pone.0047257 E