Myc and Fgf Are Required for Zebrafish Neuromast Hair Cell Regeneration.

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PloS one, ISSN: 1932-6203, Vol: 11, Issue: 6, Page: e0157768

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10.1371/journal.pone.0157768; 10.1371/journal.pone.0157768.g004; 10.1371/journal.pone.0157768.g005; 10.1371/journal.pone.0157768.g003; 10.1371/journal.pone.0157768.g001; 10.1371/journal.pone.0157768.g002
Sang Goo Lee; Mingqian Huang; Nikolaus D. Obholzer; Shan Sun; Wenyan Li; Marco Petrillo; Pu Dai; Yi Zhou; Douglas A. Cotanche; Sean G. Megason; Huawei Li; Zheng-Yi Chen; Olivia Bermingham-McDonogh Show More Hide
Public Library of Science (PLoS); Figshare
Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Medicine; Cell Biology; Genetics; Molecular Biology; Neuroscience; Physiology; Evolutionary Biology; Developmental Biology; Cancer; Hematology; hair cells; MYC; hair cell precursors; hair cell loss; line neuromast hair cell regeneration model; chick hair cell regeneration; anterior-posterior fgfr 1a; FGF; Zebrafish Neuromast Hair Cell Regeneration; fgfr 1a; hair cell regeneration
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Unlike mammals, the non-mammalian vertebrate inner ear can regenerate the sensory cells, hair cells, either spontaneously or through induction after hair cell loss, leading to hearing recovery. The mechanisms underlying the regeneration are poorly understood. By microarray analysis on a chick model, we show that chick hair cell regeneration involves the activation of proliferation genes and downregulation of differentiation genes. Both MYC and FGF are activated in chick hair cell regeneration. Using a zebrafish lateral line neuromast hair cell regeneration model, we show that the specific inhibition of Myc or Fgf suppresses hair cell regeneration, demonstrating that both pathways are essential to the process. Rapid upregulation of Myc and delayed Fgf activation during regeneration suggest a role of Myc in proliferation and Fgf in differentiation. The dorsal-ventral pattern of fgfr1a in the neuromasts overlaps with the distribution of hair cell precursors. By laser ablation, we show that the fgfr1a-positive supporting cells are likely the hair cell precursors that directly give rise to new hair cells; whereas the anterior-posterior fgfr1a-negative supporting cells have heightened proliferation capacity, likely to serve as more primitive progenitor cells to replenish lost precursors after hair cell loss. Thus fgfr1a is likely to mark compartmentalized supporting cell subtypes with different capacities in renewal proliferation and hair cell regeneration. Manipulation of c-MYC and FGF pathways could be explored for mammalian hair cell regeneration.