Abstract
The heart is the first functional organ to form during vertebrate development. Congenital heart defects are the most common type of human birth defect, many originating as anomalies in early heart development. The zebrafish model provides an accessible vertebrate system to study early heart morphogenesis and to gain new insights into the mechanisms of congenital disease. Although composed of only two chambers compared with the four-chambered mammalian heart, the zebrafish heart integrates the core processes and cellular lineages central to cardiac development across vertebrates. The rapid, translucent development of zebrafish is amenable to in vivo imaging and genetic lineage tracing techniques, providing versatile tools to study heart field migration and myocardial progenitor addition and differentiation. Combining transgenic reporters with rapid genome engineering via CRISPR-Cas9 allows for functional testing of candidate genes associated with congenital heart defects and the discovery of molecular causes leading to observed phenotypes. Here, we summarize key insights gained through zebrafish studies into the early patterning of uncommitted lateral plate mesoderm into cardiac progenitors and their regulation. We review the central genetic mechanisms, available tools, and approaches for modeling congenital heart anomalies in the zebrafish as a representative vertebrate model.
Highlights
Zebrafish to Study Earliest Heart DevelopmentPowerful genetic tools, rapid external embryonic development, optical transparency of the embryo, and a high number of offspring render the zebrafish (Danio rerio) an increasingly common vertebrate system for studying development and for modeling human disease [1,2]
By 3–5 days post-fertilization, the zebrafish heart principally features an inflow tract (IFT) portion, atrium, a trabeculated ventricle separated by a tricuspid valve [20,26], an outflow tract region encompassing the distal ventricle and ending in the smooth musclebased bulbus arteriosus (BA) that acts as pressure capacitator [27,28], and a complex functional conduction system regulated by the cardiac pacemaker of the sinus venosus at the IFT [29] (Figure 1D)
While tetrapod-specific adaptations such as septation or formation of a pulmonary circuit are out of direct reach of study in the model, zebrafish have contributed to establishing basic concepts of early heart field emergence and patterning in vertebrates
Summary
Rapid external embryonic development, optical transparency of the embryo, and a high number of offspring render the zebrafish (Danio rerio) an increasingly common vertebrate system for studying development and for modeling human disease [1,2]. By 3–5 days post-fertilization (dpf), the zebrafish heart principally features an inflow tract (IFT) portion, atrium, a trabeculated ventricle separated by a tricuspid valve [20,26], an outflow tract region encompassing the distal ventricle and ending in the smooth musclebased bulbus arteriosus (BA) that acts as pressure capacitator [27,28], and a complex functional conduction system regulated by the cardiac pacemaker of the sinus venosus at the IFT [29] (Figure 1D) This astonishingly rapid and accessible development in a vertebrate embryo has enabled previously unprecedented experiments to understand the earliest processes leading to cardiac progenitor patterning within the LPM and initial morphogenesis of the heart
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