Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration
Abstract Background Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmamm...
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doaj-efbaac5aa13946c6a9dcd1146bedd62e2020-11-24T23:29:37ZengBMCBMC Neuroscience1471-22022017-08-0118111010.1186/s12868-017-0382-zMusashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regenerationTakahiro Wakasaki0Hiroaki Niiro1Siamak Jabbarzadeh-Tabrizi2Mitsuru Ohashi3Takashi Kimitsuki4Takashi Nakagawa5Shizuo Komune6Koichi Akashi7Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu UniversityAbstract Background Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells. Results In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p = 0.05, Benjamini–Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the downstream genes in the Notch pathway. Higher expression of these genes in supporting cells compared with that in hair cells was confirmed by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry analysis demonstrated that MSI1 was mainly localized at the basal side of the supporting cell layer in normal chick utricles. During the regeneration period following aminoglycoside antibiotic-induced damage of chicken utricles, the expression levels of MSI1, hairy and enhancer of split-5, and cyclin D1 were increased, and BrdU labeling indicated that cell proliferation was enhanced. Conclusions The findings of this study suggested that MSI1 played an important role in the proliferation of supporting cells in the inner ear during normal and damaged conditions and could be a potential therapeutic target in the treatment of vestibular defects.http://link.springer.com/article/10.1186/s12868-017-0382-zMusashi-1Chick inner earRegenerationcDNA microarrayLaser capture microdissection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takahiro Wakasaki Hiroaki Niiro Siamak Jabbarzadeh-Tabrizi Mitsuru Ohashi Takashi Kimitsuki Takashi Nakagawa Shizuo Komune Koichi Akashi |
spellingShingle |
Takahiro Wakasaki Hiroaki Niiro Siamak Jabbarzadeh-Tabrizi Mitsuru Ohashi Takashi Kimitsuki Takashi Nakagawa Shizuo Komune Koichi Akashi Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration BMC Neuroscience Musashi-1 Chick inner ear Regeneration cDNA microarray Laser capture microdissection |
author_facet |
Takahiro Wakasaki Hiroaki Niiro Siamak Jabbarzadeh-Tabrizi Mitsuru Ohashi Takashi Kimitsuki Takashi Nakagawa Shizuo Komune Koichi Akashi |
author_sort |
Takahiro Wakasaki |
title |
Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration |
title_short |
Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration |
title_full |
Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration |
title_fullStr |
Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration |
title_full_unstemmed |
Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration |
title_sort |
musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration |
publisher |
BMC |
series |
BMC Neuroscience |
issn |
1471-2202 |
publishDate |
2017-08-01 |
description |
Abstract Background Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells. Results In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p = 0.05, Benjamini–Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the downstream genes in the Notch pathway. Higher expression of these genes in supporting cells compared with that in hair cells was confirmed by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry analysis demonstrated that MSI1 was mainly localized at the basal side of the supporting cell layer in normal chick utricles. During the regeneration period following aminoglycoside antibiotic-induced damage of chicken utricles, the expression levels of MSI1, hairy and enhancer of split-5, and cyclin D1 were increased, and BrdU labeling indicated that cell proliferation was enhanced. Conclusions The findings of this study suggested that MSI1 played an important role in the proliferation of supporting cells in the inner ear during normal and damaged conditions and could be a potential therapeutic target in the treatment of vestibular defects. |
topic |
Musashi-1 Chick inner ear Regeneration cDNA microarray Laser capture microdissection |
url |
http://link.springer.com/article/10.1186/s12868-017-0382-z |
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