Heart Development and Regeneration in Non-mammalian Model Organisms

Abstract

Cardiovascular disease is a serious threat to human health and a leading cause of mortality worldwide. Recent years have witnessed exciting progress in the understanding of heart formation and development, enabling cardiac biologists to make significant advance in the field of therapeutic heart regeneration. Most of our understanding of heart development and regeneration, including the genes and signaling pathways, are driven by pioneering works in non-mammalian model organisms, such as fruit fly, fish, frog, and chicken. Compared to mammalian animal models, non-mammalian model organisms have special advantages in high-throughput applications such as disease modeling, drug discovery, and cardiotoxicity screening. Genetically engineered animals of cardiovascular diseases provide valuable tools to investigate the molecular and cellular mechanisms of pathogenesis and to evaluate therapeutic strategies. A large number of congenital heart diseases (CHDs) non-mammalian models have been established and tested for the genes and signaling pathways involved in the diseases. Here, we reviewed the mechanisms of heart development and regeneration revealed by these models, highlighting the advantages of non-mammalian models as tools for cardiac research. The knowledge from these animal models will facilitate therapeutic discoveries and ultimately serve to accelerate translational medicine.

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

“…In zebrafish, blood flows into a single atrium, which is connected to a single ventricle by an atrio-ventricular valve [41]. The ventricle pumps blood into circulation through a prominent outflow tract called the bulbus arteriosus [10].…”

“…The absence of cardiac regeneration in humans has focused the attention of many researchers towards non-mammalian species [10,42,43]. Several studies have established a great efficiency among zebrafish in their capacity for cardiac regeneration throughout their life which can be harnessed to develop novel insights in investigating similar processes in humans [44,45].…”

“…Over the years, there has been a widespread increase in the use of zebrafish as a popular model for research on developmental biology. This popularity can largely be attributed to the presence of human gene orthologs in zebrafish, as well as an abundance of samples due to their large brood sizes and more accelerated life cycle than that of mammals [10,11]. Zebrafish are also amenable to sophisticated microscopy and imaging procedures.…”

“…Because zebrafish undergo external fertilization and are transparent during early developmental stages, zebrafish growth during specific developmental windows can be monitored in real-time. 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]. Elegant mutational techniques such as CRISPR are also easy to employ.…”

“…Regeneration in the context of zebrafish, or teleosts which are fish with fully movable maxilla and premaxilla, was first documented 235 years ago [16]. Over the last several decades, many studies have proven zebrafish to be an excellent model for studying regeneration, especially in relation to cardiac biology [10,[17][18][19][20][21][22][23].…”