PMC:3886832 / 1512-4208 JSONTXT

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Introduction\nHearing and vestibular impairment can be caused by the loss of sensory hair cells in the inner ear of vertebrates. These hair cells can be damaged and/or lost by exposure to loud or prolonged sound [1,2,3], ototoxic drugs [4] and disease and aging [5]. Hair cell loss in humans and other mammals is permanent, but regeneration of lost hair cells occurs spontaneously in non-mammalian vertebrates, including fish [6,7,8,9], amphibians [10,11], reptiles [12] and birds [13,14,15,16] (also, see review in [17]). This potential for the production of new hair cells in non-mammalian vertebrates has been known since the 1930s, when the regeneration of the lateral line hair cells on amphibian tails was studied [18,19]. Later, in the 1980s, it was discovered that new hair cells were formed in the inner ears of adult cartilaginous and bony fishes [20,21,22] and that birds could regenerate new hair cells following damage-induced loss of hair cells in the basilar papillae [13,14,15,16,23].\nSince these earlier discoveries, researchers have been examining the process of hair cell death and regeneration in non-mammalian animals, in an attempt to find ways of stimulating the production of new hair cells in mammals. The ultimate goal of this research is to find new therapeutics for human sensorineural hearing and balance deficits. Recent advances in molecular biology techniques have assisted in this search. Gene expression profiling of inner ear tissues has been useful in discovering cellular pathways that are regulated during the process of hair cell death and regeneration. With this technique, scientists have identified genes that are up- or downregulated in comparison to different time points following trauma to the inner ear [24,25,26] or between sensory tissue types that differ in terms of normal cell proliferation (e.g., the mammalian utricle vs. cochlea) [27] or between different cell types within a single sensory organ [28]. \nThe technologies for examining such patterns have evolved rapidly—from dot blots to microarray analysis, to next-generation sequencing (NGS) and microRNA analysis [29]. Simultaneously, techniques for protein separation and characterization have also improved, increasing the role of proteomics in understanding processes in the inner ear [30]. This article reviews the methods that have been used in an attempt to find cellular pathways that are regulated during the process of hair cell regeneration in vertebrates and discusses the results of representative studies using these methods in an effort to find common pathways important to hair cell regeneration and potential therapeutic targets to treat deafness and balance disorders."}