Myc and Fgf Are Required for Zebrafish Neuromast Hair Cell Regeneration
| Autor: | Marco Petrillo, Shan Sun, Mingqian Huang, Nikolaus D. Obholzer, Huawei Li, Wenyan Li, Zheng-Yi Chen, Pu Dai, Douglas A. Cotanche, Sang Goo Lee, Yi Zhou, Sean G. Megason |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microarrays Lateral line lcsh:Medicine Gene Expression Fibroblast growth factor Larvae Antibiotics Medicine and Health Sciences Mast Cells Cell Cycle and Cell Division lcsh:Science Zebrafish In Situ Hybridization Multidisciplinary biology integumentary system Antimicrobials Fishes Drugs Neomycins Animal Models Cell biology medicine.anatomical_structure Bioassays and Physiological Analysis Osteichthyes Cell Processes Vertebrates Inner Ear Hair cell Anatomy Research Article Molecular Probe Techniques Research and Analysis Methods Microbiology Proto-Oncogene Proteins c-myc 03 medical and health sciences Model Organisms Microbial Control medicine otorhinolaryngologic diseases Genetics Animals Regeneration Neurons Afferent Progenitor cell Molecular Biology Techniques Molecular Biology Cell Proliferation Pharmacology Metamorphosis Cell growth Regeneration (biology) lcsh:R Organisms Biology and Life Sciences Cell Biology Zebrafish Proteins biology.organism_classification Receptors Fibroblast Growth Factor Probe Hybridization Lateral Line System Fibroblast Growth Factors 030104 developmental biology Ears lcsh:Q sense organs Developmental biology Head Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 6, p e0157768 (2016) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|