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Myc and Fgf Are Required for Zebrafish Neuromast Hair Cell Regeneration.
- Source :
-
PloS one [PLoS One] 2016 Jun 28; Vol. 11 (6), pp. e0157768. Date of Electronic Publication: 2016 Jun 28 (Print Publication: 2016). - Publication Year :
- 2016
-
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.
- Subjects :
- Animals
Cell Proliferation
Fibroblast Growth Factors genetics
Lateral Line System cytology
Lateral Line System physiology
Mast Cells cytology
Mast Cells physiology
Neurons, Afferent cytology
Neurons, Afferent physiology
Proto-Oncogene Proteins c-myc genetics
Receptors, Fibroblast Growth Factor genetics
Receptors, Fibroblast Growth Factor metabolism
Zebrafish
Zebrafish Proteins genetics
Zebrafish Proteins metabolism
Fibroblast Growth Factors metabolism
Lateral Line System metabolism
Mast Cells metabolism
Neurons, Afferent metabolism
Proto-Oncogene Proteins c-myc metabolism
Regeneration
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27351484
- Full Text :
- https://doi.org/10.1371/journal.pone.0157768