Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration

BMC Neuroscience

Research Article

Hiroaki Niiro¹  Siamak Jabbarzadeh-Tabrizi¹  Koichi Akashi¹  Takashi Nakagawa²  Shizuo Komune²  Takashi Kimitsuki²  Mitsuru Ohashi²  Takahiro Wakasaki³ 

[1]Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

[2]Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

[3]Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

[4]Department of Head and Neck Surgery, National Hospital Organization, Kyushu Cancer Center, 3-1-1 Notame, Miniami-ku, 811-1395, Fukuoka, Japan

关键词: Musashi-1;    Chick inner ear;    Regeneration;    cDNA microarray;    Laser capture microdissection;   

DOI  :  10.1186/s12868-017-0382-z

 received in 2017-01-02, accepted in 2017-08-10,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundHair 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.ResultsIn 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s) 2017