Perspective

This special issue of Developmental Dynamics focuses on zebrafish, one of the newest model organisms for learning mechanisms underlying vertebrate development and function. Even a decade ago, it would have been unthinkable to focus an entire journal issue on zebrafish. What features led to the meteoric rise in popularity of this model? George Streisinger’s landmark article demonstrating that simple physical treatments could be used to produce clones of homozygous diploid zebrafish was featured on the cover of Nature 22 years ago (Streisinger et al., 1981; Fig. 1) and celebrated publically by a cartoon in the Chicago Tribune (Fig. 2). This work heralded the dawn of a new era in which genes required for development and functioning of vertebrates could be revealed by classical forward genetic screens for mutant phenotypes. Although such screens had been carried out for many years in multicellular invertebrate animals, in particular fruit flies and nematode worms, the difficulty of driving recessive mutations to homozygosity had essentially precluded this type of genetic approach in vertebrates. The genetic potential suggested by Streisinger was realized in the mid-1990s by publication of a series of studies reporting on large-scale screens for phenotypes based on morphological changes in the shape of the embryo (Haffter et al., 1996; Driever et al., 1996) as well as smaller screens for phenotypes based on changes in the expression patterns of molecular markers (Moens et al., 1996; Henion et al., 1996). At the same time Streisinger was perfecting genetic methods for zebrafish, several of his University of Oregon colleagues were developing techniques for imaging and manipulating cells within the living zebrafish embryo. A series of publications from the mid-1980s to early 1990s demonstrated the ability to fate map cells at a variety of different stages of embryogenesis (Kimmel and Warga, 1988), to label and transplant cells individually and follow their developmental fates (Westerfield and Eisen, 1988; Eisen, 1991; Ho and Kimmel, 1993), and to test the requirement for gene function in chimeras by transplanting specific cells between embryos of different genotypes (Ho and Kane, 1990; Eisen and Pike, 1991). The ability to couple genetics and superb embryology in zebrafish propelled this model into the limelight. Studies from other models revealed that in addition to forward genetics, molecular approaches, including the ability to manipulate expression of known genes, provided powerful approaches for investigating vertebrate development and function. Mapping of the zebrafish genome (Postlethwait et al., 1994), creation of the first transgenic zebrafish (Stuart et al., 1988), cloning of the first zebrafish genes defined by mutations using candidate gene (Schulte-Merker et al., 1994), and positional cloning (Zhang et al., 1998) strategies and knockdown of the first gene using morpholino antisense oligonucleotides (Nasevicius and Ekker, 2000) established the necessary molecular and genomic tools in zebrafish. The importance of these approaches is highlighted by the Trans-NIH Zebrafish Initiative promoting the use of zebrafish as a model organism for the study of vertebrate development and disease (http://www.nih.gov/science/models/ zebrafish/). This special issue of Development Dynamics provides ample evidence of the breadth of contributions made by studies of zebrafish, using the genetic, embryological, genomic, and molecular approaches developed over the past 22 years. Review articles here address a broad range of issues, including development and application of genetic and genomic tools, genetic screens, development and patterning of body organs, and the potential of zebrafish as a model in which to uncover mechanisms underlying human genetic diseases. One of the most exciting advances of the past century was the realization that common genes program development of animals with dispar-