Zebrafish models in cardiac development and congenital heart birth defects

Abstract

The zebrafish has become an ideal vertebrate animal system for investigating cardiac development due to its genetic tractability, external fertilization, early optical clarity and ability to survive without a functional cardiovascular system during development. In particular, recent advances in imaging techniques and the creation of zebrafish transgenics now permit the in vivo analysis of the dynamic cellular events that transpire during cardiac morphogenesis. As a result, the combination of these salient features provides detailed insight as to how specific genes may influence cardiac development at the cellular level. In this review, we will highlight how the zebrafish has been utilized to elucidate not only the underlying mechanisms of cardiac development and human congenital heart diseases (CHDs), but also potential pathways that may modulate cardiac regeneration. Thus, we have organized this review based on the major categories of CHDs – structural heart, functional heart, and vascular/great vessel defects, and will conclude with how the zebrafish may be further used to contribute to our understanding of specific human CHDs in the future.

Temporal cohesion of the structural, functional and molecular characteristics of the developing zebrafish heart

“…According to VonBaer (1828) (as cited by Moorman and Christoffels (2003)), it is the embryonic rather than the adult heart that should be compared since the common features of a vertebrate group appear early in development. In the last twenty years the zebrafish (Danio rerio) has emerged as a powerful and increasingly popular model to study cardiac development (Hu et al, 2000;Bakkers, 2011) and cardiac defects (Antkiewicz et al, 2005;Tu and Chi, 2012). Forward genetic screens have identified many novel regulatory mechanisms with essential roles in cardiogenic specification and Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/diff differentiation, migration of cardiac progenitor cells, heart tube morphogenesis, and cardiac function (Harvey, 2002).…”

An Exploratory Analysis of Stream Teratogenicity and Human Health Using Zebrafish Whole-Sediment Toxicity Test

“…Despite these limitations, there remains an incentive to investigate CHD in an ecologic context with zebrafish. Though structurally distinct from human hearts, zebrafish cardiogenesis is often proposed as a useful model for understanding human cardiovascular development [45][46][47]. TCDD dosing, for example, has been linked to heart malformation in zebrafish embryos [63].…”

“…In this study a relationship was observed between the PC1 (which seemed to represent a lingering, generalized stress-response) at 72HPF and infant mortality (which is often cited as a generalized population health metric). Zebrafish have also been utilized to elucidate underlying mechanisms of cardiac development and human congenital heart diseases, as well as potential pathways that may modulate cardiac regeneration [45][46][47]. It therefore stands to reason that, despite obvious structural differences between fish and mammal hearts, PC3 could indicate a response that is analogous to pathways producing human CHD.…”

Block the function of nonmuscle myosin II by blebbistatin induces zebrafish embryo cardia bifida

“…The bilateral cardiomyocytes then migrate toward the midline and fuse to form a cone-shaped heart at the 21-somite stage. Subsequently, the heart cone begins to elongate and forms a single heart tube at 24 hpf (Stainier 2001;Bakkers 2011;Miura and Yelon 2011;Tu and Chi 2012). One type of heart mutant bears two swollen pericardial sacs with a beating structure in each one of them, which are known as cardia bifida phenotype (Chen et al 1996;Stainier et al 1996).…”