title: Myc and Fgf Are Required for Zebrafish Neuromast Hair Cell Regeneration.
abstract: 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.
authors.affiliation: Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States of America.|Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Sang Goo
authors.identifier: http://orcid.org/0000-0002-0024-9266
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States of America.|Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Mingqian
authors.identifier: http://orcid.org/0000-0003-0870-9199
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Nikolaus D
authors.initials: ND
authors.lastname: Obholzer
authors.affiliation: Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States of America.|Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.|Department of Otorhinolaryngology, Shanghai Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States of America.|Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.|Department of Otorhinolaryngology, Shanghai Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States of America.|Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Marco
authors.initials: M
authors.lastname: Petrillo
authors.affiliation: Department of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
authors.affiliation: Stem Cell Program and Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Cotanche
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sean G
authors.initials: SG
authors.lastname: Megason
authors.affiliation: Department of Otorhinolaryngology, Shanghai Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States of America.|Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D053403:Lateral Line System / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D017468:Receptors, Fibroblast Growth Factor; D029961:Zebrafish Proteins; D005346:Fibroblast Growth Factors