Abstract

BackgroundThe mammalian inner ear contains sensory organs, the organ of Corti in the cochlea and cristae and maculae in the vestibule, with each comprised of patterned sensory epithelia that are responsible for hearing and balance. The development, cell fate, patterning, and innervation of both the sensory and nonsensory regions of the inner ear are governed by tight regulation involving, among others, transcription factors and microRNAs (miRNAs). In humans, mutations in specific miRNA genes are associated with hearing loss. In mice, experimental reduction or mutations of miRNAs in the inner ear leads to severe developmental and structural abnormalities. A comprehensive identification of miRNAs in the sensory epithelia and their gene targets will enable pathways of auditory and vestibular function to be defined.ResultsIn this study, we used Next-Generation Sequencing (NGS) to identify the most prominent miRNAs in the inner ear and to define miRNA-target pairs that form pathways crucial for the function of the sensory epithelial cells. NGS of RNA from inner ear sensory epithelial cells led to the identification of 455 miRNAs in both cochlear and vestibular sensory epithelium, with 30 and 44 miRNAs found in only cochlea or vestibule, respectively. miR-6715-3p and miR-6715-5p were defined for the first time in the inner ear. Gene targets were identified for each of these miRNAs, including Arhgap12, a GTPase activating protein, for miR-6715-3p, implicating this miRNA in sensory hair cell bundle development, actin reorganization, cell adhesion and inner ear morphogenesis.ConclusionsThis study provides a comprehensive atlas of miRNAs in the inner ear sensory epithelia. The results provide further support of the essential regulatory role of miRNAs in inner ear sensory epithelia and in regulating pathways that define development and growth of these cells.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-484) contains supplementary material, which is available to authorized users.

Highlights

  • The mammalian inner ear contains sensory organs, the organ of Corti in the cochlea and cristae and maculae in the vestibule, with each comprised of patterned sensory epithelia that are responsible for hearing and balance

  • By binding to sequences in the 3’ untranslated region (UTR) of mRNAs, a miRNA can inhibit target mRNAs by translational suppression and mRNA destabilization [2]. miRNAs have been implicated in hearing loss in humans, since mutations in the

  • The sensory epithelium consisted of the organ of Corti, including hair cells, supporting cells, and cells of the greater and lesser epithelial ridges, as well as mesenchymal and neuronal cells

Read more

Summary

Introduction

The mammalian inner ear contains sensory organs, the organ of Corti in the cochlea and cristae and maculae in the vestibule, with each comprised of patterned sensory epithelia that are responsible for hearing and balance. MiRNAs have been implicated in hearing loss in humans, since mutations in the to the alteration in expression and function of both direct and indirect gene targets [9]. A number of mouse mutants affecting miRNA regulation through Dicer have been created, leading to developmental inner ear defects [10,11] These conditional knock-out mouse mutants have been instrumental in demonstrating that miRNAs are vital for inner ear morphogenesis and development of the sensory epithelia and sensory neurons. The miR-6715-3p–Arhgap miRNA target pair defines a new regulatory pathway Understanding these interactions may shed light on known and novel miRNAs, their effect on the development of normal and impaired hearing, and the mechanisms leading towards deafness

Methods
Results
Discussion
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.