Vascular development in zebrafish

The use of zebrafish (Danio rerio) as a vertebrate model has yielded tremendous insight into the complex cellular and molecular events that underlie embryonic vascular development. Compared to more traditional model organisms such as chicks, mice, and frogs, zebrafish offer distinct advantages and have made unique contributions toward our understanding of vascular development. Recent studies in zebrafish have led to the identification of mutations and molecules that are responsible for the specification of endothelial progenitor cells (or angioblasts), differentiation of arterial and venous cells, and patterning of the dorsal aorta (DA) and intersegmental vessels. Zebrafish embryos develop externally and are optically clear, affording noninvasive and high-resolution access to nearly the entire vascular system. The ability of zebrafish embryos to survive temporarily without blood circulation (oxygen is obtained via diffusion) permits the study of defects in vascular development that would otherwise be embryonic lethal in other organisms, and without the confounding effects of hypoxia. Given their fecundity, small size, and brief generation time, zebrafish are highly amenable to genetic manipulation, including large-scale mutagenesis screens. Importantly, the zebrafish genome has been mapped and sequenced by the Sanger Center in Britain. Genomic and positional cloning reagents, such as genetic maps and libraries, are available. Forward genetic approaches, in combination with gene mapping and positional cloning, already have been employed successfully to identify genes that disrupt the formation and patterning of embryonic vasculature and other organs (1,2). The discovery of gridlock (grl) – a hairy-related basic helix-loop-helix (bHLH) transcription factor involved in arterial endothelial development – demonstrates the power of mutagenesis screens to uncover novel genetic pathways and developmental mechanisms with no presupposition about the role of genes in biological processes (discussed below) (3,4).