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J.-N. Chen and M. C. Fishman
patterning [for review see Pattern Fonnation during Development
(1997) Cold Spring Harbor Symposium Quantum Biology, vol. 62].
Zebrafish has recently attracted significant attention from vertebrate
developmental biologists, because it is amenable to both embryological
and genetics studies. DNAIRNA injections, cell transplantation, in vivo
time-lapse analysis, and lineage-tracing techniques are routinely used to
analyze gene function and developmental processes in the zebrafish. In
general, each pair of fish produces hundreds of progeny every week. The
embryo is fertilized outside of the body and is transparent. Therefore,
developmental processes can be followed from the single-cell stage to
the time when organs are fully fonned and functional. This makes
zebrafish uniquely suitable for large-scale ·vertebrate genetic screens.
Two large-scale genetic screens have been perfonned and more than two
thousand mutations affecting specific developmental processes have
been identified (Driever et al. 1996; Haffter et al. 1996). Recent progress
in assembling genomic resources facilitates the cloning of these mutations.
Zebrafish is especially suited to studies of the embryonic heart. A
functional heart is present in a prominent ventral location in the zebrafish embryo 24 hours after fertilization. The fish heart, like the heart
of other vertebrates, consists of two major cell types, myocardium and
endocardium, derived from precursors, bilateral mesodermal primordia.
Soon after fusion, a border forms between what will become the atrium
and the ventricle. In mammals and birds, septae later grow to subdivide
both the embryonic atrium and the embryonic ventricle, generating a
four-chambered heart. The ventricle later bends towards the right side of
the embryo in the zebrafish starting at 33 hours after fertilization. This
process is referred to as cardiac looping, and occurs in the heart of all
vertebrates. After 2 days of development in the zebrafish, the ventricular
myocardial layer differentiates into a thick-walled chamber, and is capable of generating systemic blood pressure. The valves start to differentiate at the borders of the chambers after 3 days of development to prevent
backflow of blood (Chen and Fishman 1997). We have discovered in
two large-scale genetic screens, mutations which affect each of the steps
of heart morphogenesis, as well as its functional development of rate,
rhythm, conduction, and contractility (Chen et al. 1996; Stainier et al.
1996).
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