Genetic models of cancer in zebrafish.
Firmly established as a model system for development, the zebrafish is now emerging as an effective system for the study of the fundamental aspects of tumorigenesis. In keeping with the striking anatomical and physiological similarity between fish and mammals, zebrafish develop a wide spectrum of cancers resembling human malignancies. The potential for zebrafish as a cancer model derives from its strengths as an experimental system for developmental biology. Despite 450 million years of evolutionary distance, the pathways that govern vertebrate development including signaling, proliferation, cell movements, differentiation, and apoptosis-indeed, the same pathways that are often misregulated in tumorigenesis-are highly conserved between humans and zebrafish. This, together with a complete genome sequence and an array of tools for gene manipulation, makes the construction of robust, physiological zebrafish cancer models increasingly possible.