Advances in Cardiac Development and Regeneration Using Zebrafish as a Model System for High-Throughput Research.

Nicholas Francoeur,Rwik Sen

doi:10.3390/jdb9040040

Abstract

Heart disease is the leading cause of death in the United States and worldwide. Understanding the molecular mechanisms of cardiac development and regeneration will improve diagnostic and therapeutic interventions against heart disease. In this direction, zebrafish is an excellent model because several processes of zebrafish heart development are largely conserved in humans, and zebrafish has several advantages as a model organism. Zebrafish transcriptomic profiles undergo alterations during different stages of cardiac development and regeneration which are revealed by RNA-sequencing. ChIP-sequencing has detected genome-wide occupancy of histone post-translational modifications that epigenetically regulate gene expression and identified a locus with enhancer-like characteristics. ATAC-sequencing has identified active enhancers in cardiac progenitor cells during early developmental stages which overlap with occupancy of histone modifications of active transcription as determined by ChIP-sequencing. CRISPR-mediated editing of the zebrafish genome shows how chromatin modifiers and DNA-binding proteins regulate heart development, in association with crucial signaling pathways. Hence, more studies in this direction are essential to improve human health because they answer fundamental questions on cardiac development and regeneration, their differences, and why zebrafish hearts regenerate upon injury, unlike humans. This review focuses on some of the latest studies using state-of-the-art technology enabled by the elegant yet simple zebrafish.

Highlights

Zebrafish is an excellent model system for research on developmental biology, and this model has been used in highly impactful studies that have defined the field
The results showed that the green fluorescent protein (GFP)-positive cells contain 155,879 ATAC-seq peaks which correlate to regions of open or accessible chromatin
Another study used CRISPR in a pioneering approach towards precise gene editing in zebrafish, to reveal cardiac developmental roles of a DNA-binding factor called pbx3 [107], whose single nucleotide variant is associated with human disease

Summary

Introduction

Zebrafish is an excellent model system for research on developmental biology, and this model has been used in highly impactful studies that have defined the field. There has been a widespread increase in the use of zebrafish as a popular model for research on developmental biology. Zebrafish are likewise advantageous for forward and reverse genetics studies [12], because it is convenient to employ sophisticated techniques to create mutations [13] and transgenic reporter lines [10,14,15]. With increasing focus on genome-wide profiling of transcriptomic and epigenomic landscapes, studies on heart development and regeneration in zebrafish have started employing high-throughput techniques using next-generation sequencing to address the above questions. We explore the specific contributions of the zebrafish model to cardiac development and regeneration research involving state-of-the-art technology for high-throughput transcriptomic and epigenomic profiling

Zebrafish Heart Development

Epigenomic Mapping of Zebrafish Reveals New Insights into Cardiac Development

Conclusions

Findings

Methods