Insights into inner ear-specific gene regulation: Epigenetics and non-coding RNAs in inner ear development and regeneration.
The vertebrate inner ear houses highly specialized sensory organs, tuned to detect and encode sound, head motion and gravity. Gene expression programs under the control of transcription factors orchestrate the formation and specialization of the non-sensory inner ear labyrinth and its sensory constituents. More recently, epigenetic factors and non-coding RNAs emerged as an additional layer of gene regulation, both in inner ear development and disease. In this review, we provide an overview on how epigenetic modifications and non-coding RNAs, in particular microRNAs (miRNAs), influence gene expression and summarize recent discoveries that highlight their critical role in the proper formation of the inner ear labyrinth and its sensory organs. Finally, we discuss recent insights into how epigenetic factors and miRNAs may facilitate, or in the case of mammals, restrict inner ear sensory hair cell regeneration.
The Solomon H. Snyder Department of Neuroscience, the Center for Sensory Biology, the Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA. Electronic address: adoetzlhofer@jhmi.edu.
Angelika
A
Doetzlhofer
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: karena@post.tau.ac.il.
Karen B
KB
Avraham
D000818:Animals; D002454:Cell Differentiation; D002642:Chick Embryo; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D051857:Otx Transcription Factors / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration / Q000235:genetics
D002843:Chromatin; C513182:Gbx2 protein, mouse; D006657:Histones; D018398:Homeodomain Proteins; D035683:MicroRNAs; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse
DNA methylation; Deafness; Hair cell regeneration; Histone modification; Inner ear development; microRNA