Using zebrafish as a model to study the role of epigenetics in hearing loss

ABSTRACT

Introduction: The rapid progress of bioinformatics and high-throughput screening techniques in recent years has led to the identification of many candidate genes and small-molecule drugs that have the potential to make significant contributions to our understanding of the developmental and pathological processes of hearing, but it remains unclear how these genes and regulatory factors are coordinated. Increasing evidence suggests that epigenetic mechanisms are essential for establishing gene expression profiles and likely play an important role in the development of inner ear and in the pathology of hearing-associated diseases. Zebrafish are a valuable and tractable in vivo model organism for monitoring changes in the epigenome and for identifying new epigenetic processes and drug molecules that can influence vertebrate development.

Areas covered: In this review, the authors focus on zebrafish as a model to summarize recent findings concerning the roles of epigenetics in the development, regeneration, and protection of hair cells.

Expert opinion: Using the zebrafish model in combination with high-throughput screening and genome-editing technologies to investigate the function of epigenetics in hearing is crucial to help us better understand the molecular and genetic mechanisms of auditory development and function. It will also contribute to the development of new strategies to restore hearing loss.

KEYWORDS:

• Hearing loss
• screening
• epigenetics
• zebrafish

Article highlights

• Zebrafish are a prominent in vivo vertebrate model in hearing research.

• Epigenomics, particularly histone modifications and DNA methylation, is an emerging discipline that identifies chemical class-specific epigenetic footprints that have the potential to allow for retrospective biomonitoring.

• High-throughput screening provides a powerful strategy to identify specific small-molecule epigenetic inhibitors and novel genes involved in epigenetic processes as potential therapeutic targets.

• The zebrafish has emerged as a powerful model for whole-organism small-molecule chemical screening and high-throughput genetic screening to aid in hearing assessment and therapeutics.

• The integration of high-throughput screening technologies, CRISPR/Cas9 systems, bioinformatics, and epigenomics can help meet the challenge of preventing and treating hearing loss.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors of this manuscript are supported by the National Natural Science Foundation of China (Nos. 81620108005, 81230019, 81500784, 81470687), the Biomedical Program of Shanghai Committee of Science and Technology (14DJ1400203), the National Science and Technology Major Project (2016YFC0905200), and the Major State Basic Research (973 Program, No. 2011CB504500). They are also supported by the National Key Research and Development Program of China (2017YFA0103900).