Considering the Zebrafish in a Comparative Context THOMAS F. SCHILLING 1Ã AND JACQUELINE WEBB 2 1 Department of Developmental and Cell Biology, University of California, Irvine, California 2 Department of Biological Sciences, University of Rhode Island, Kingston, Rhode Island ABSTRACT This article introduces a special issue on zebrafish biology that attempts to integrate developmental genetics with comparative studies of other fish species. For zebrafish researchers, comparative work offers a better understanding of the evolutionary history of their model system. Comparative biologists can gain many insights from the developmental and genetic mechanisms revealed in zebrafish that have contributed to the huge range of morphological variation among fishes that has arisen over millions of years. These ideas are considered here in various contexts, including systematics, genome organization and the development of the nervous system, pigmentation, craniofacial skeleton and dentition. Studies of the zebrafish in phylogenetic context provide an opportunity for synergy between communities using these two fundamentally different approaches. J. Exp. Zool. (Mol. Dev. Evol.) 308B:515– 522, 2007. r 2007 Wiley-Liss, Inc. How to cite this article: Schilling TF, Webb J. 2007. Considering the zebrafish in a comparative context. J. Exp. Zool. (Mol. Dev. Evol.) 308B:515–522. Model species (e.g., Drosophila, Caenorhabditis elegans, zebrafish, mouse) are treated primarily as gene discovery tools and bioassays for gene function in biomedical research. The resources required to develop the genetic tools for any model organism have limited their number. Furthermore, model species are often chosen based on historical or practical reasons (easy rearing and maintenance, ability to manipulate embryos) rather than their interesting morphological characteristics or key phylogenetic positions (Bolker, ’95). The zebrafish, Danio rerio, a small minnow from the Indian subcontinent, was first purchased from pet stores in the 1970s and propagated in the laboratory for its attractive attributes such as year-round breeding, large clutch sizes and trans- parent embryos. It grew in popularity as an experimental system, and in the 1980s and 1990s, a critical mass of researchers began to develop the tools necessary to perform large-scale genetic screens and genomic analyses. Since then, the zebrafish research community has grown to include thousands of researchers, trained largely in the fields of developmental genetics and, more recently, functional genomics. The primary goal of the work carried out by these researchers is to use zebrafish to define the genetic mechanisms under- lying vertebrate development, in many cases with direct application to human health (e.g., de Jong and Zon, 2005; Grabher and Look, 2006). Despite this intense research focus, little is known about the natural history of the zebrafish (but see Engeszer et al., 2007), how its morpho- logical characteristics compare to those of closely related taxa or, until relatively recently, its phylogenetic relationships. What is not often appreciated is that the zebrafish is only one of 42,000 species of minnows (Family Cyprinidae) within the superorder Otophysi and the more inclusive Ostariophysi. The Ostariophysi repre- sent 64% of the world’s freshwater fishes and 27% of the world’s fish species (46,500 species, Nelson, 2004; www.fishbase.org). Ostariophysans (with the exception of the weakly electric Gymno- tiformes) are characterized by the production of Schreckstoff (alarm pheromone). All ostariophy- sans also possess unculi and breeding tubercles, Published online 9 August 2007 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/jez.b.21191 Received 5 July 2007; Accepted 11 July 2007 Grant sponsor: National Institutes of Health; Grant number: R-13 grant HD-52411; Grant sponsor: American Association of Anatomists Research Meeting Outreach Grant. Ã Correspondence to: Thomas F. Schilling, 4109 Natural Sciences II, Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300. E-mail: tschilli@uci.edu Minor changes have been made to article citations since this article was initially published online. r 2007 WILEY-LISS, INC. JOURNAL OF EXPERIMENTAL ZOOLOGY (MOL DEV EVOL) 308B:515–522 (2007)