Signaling and Cellular Basis of Zebrafish Neuromast Hair Cell Regeneration

来源 :第三届全国斑马鱼PI大会暨中国动物学会斑马鱼分会成立大会 | 被引量 : 0次 | 上传用户:chunhuac
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  Non-mammalian vertebrate inner ear can completely restores lost mechanosensory hair cells(HCs)through mitotic division and direct conversion of supporting cells(SCs),whereas mammalian ear possesses limited HC regeneration via these modes.The zebrafish neuromast is a mechanosensory organ,which is composed of HCs and SCs located on the animal surface,ideal for studying HC development and damage-induced HC regeneration.However,mechanisms underlying HC regeneration regulation remain elusive.We report here that neuromasts produce new HCs via direct conversion within 12h after HC damage,and subsequently through mitosis regenerate additional HCs from 24h to 72h after HC damage.Upon HC damage,a period of low Notch activity and high Wnt signaling determines direct conversion.We show that SCs at M/G1 phase of cell cycle prior to HC damage are competent to respond to regenerative cue of direct conversion,while other proliferative SCs can become mitotically regenerated HCs.Collectively,these results suggest that keeping a mitotically active SC/progenitor population in neuromast accounts for its regeneration capacity,and cell cycle states of these SCs determine the mode of HC regeneration.In a neuromast regenerative mutant that Wnt signaling is weaker due to a low level of Dvl-3,a brief boost of β-catenin level restores HC regeneration.Interestingly,all new HCs are directly converted HCs.Therefore,our study is also instructively relevant to therapeutic application of direct conversion-mediated HC regeneration.
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