cause, unlike other vertebrate model systems, adult zebrafish can be reared in large numbers (each is 5-cm long) at reasonable expense (although zebrafish are more expensive than C. elegans and Drosophila), and they are fecund, laying hundreds of eggs at regular intervals. The embryos are permeable to, and in fact, bioconcentrate many chemicals added exogenously in the water. The effects on development might be assayed simply and visually, although such tests have not been done systematically. Most important for assaying effects, the embryo is transparent and develops rapidly (128 cells develop 3-4 hours after fertilization), so all organs are visible and established during a few days. The organs, including heart, vessels, kidney, and liver, are nearly identical to those in the early human embryo. The zebrafish generation time is about 12 weeks. Its genome, carried on 26 chromosomes, is small for a vertebrate, 1,700 Mb (about half the size of the human genome).
Large-scale mutagenesis screens in zebrafish identified genes involved in development of vertebrate-specific body plans and tissues. One such chordate feature is the transient embryonic “backbone,” the notochord. The notochord generates signals (e.g., proteins of the Hedgehog family) that pattern embryonic development of adjacent tissues, including the nervous system and muscles. The neural crest is found only in vertebrates. The migratory population of neural-crest cells emanates from the neural tube and disperses widely, contributing to neural ganglia, pigmentation, jaw structures, and the major blood vessels from the heart. Other important vertebrate organ systems, without close cognates in invertebrate model genetic organisms, include the bony skeleton, an endothelial lined vascular system, a chambered heart, and gut derivatives such as the pancreas and liver, and the kidneys.
Individual mutants from large-scale screens of zebrafish were found to have perturbations in organogenesis and in other aspects of development that are highly informative. For example, the notochord is ablated entirely in some mutants, and in others, the notochord is structurally present but particular notochord signals are absent. Neural-crest derivatives, such as neurons, craniofacial structures, and melanocytes (pigment cells), are affected by mutations. Different modules of organ form or function are selectively removed by individual mutations. For example, the Pandora mutation eliminates the heart ventricle; Slo Mo causes a slow heart rate. Those mutations, therefore, provide an entrance point to specific pathways of organogenesis. In some cases, the phenotypes resemble congenital disorders, such as aortic coarctation (as noted in Chapter 2, cardiac defects are the most common of live-born human developmental defects). Others have phenotypes that are common in the adult, such as heart failure. Current screens are pinpointing even more subtle phenotypes, in part by inclusion of molecular probes to reveal particular cell populations. For example, a large number of mutants