Molecular genetics of pigmentation in the zebrafish

The zebrafish (Danio rerio) is an excellent model vertebrate due to its inherent biological and genomic complexity. In addition, this system has an extensive list of available molecular genetics tools. We have explored the use of zebrafish for modeling the formation and function of pigmentation during development. Using morpholinos for the targeted 'knock down' of tyrosinase expression, we demonstrate a conserved role of this gene in development of zebrafish pigment. As part of an ongoing collaborative morpholino screen, we have investigated other developmental processes using morpholinos as well. Through this approach, we have been successful in identifying novel, conserved genes in a variety of processes including patterning, vascular development, and lipid metabolism. In addition, we have isolated at least 3 new potential zebrafish pigmentation genes from our initial screen of 182 gene targets. One such gene, the vacuolar ATPase subunit c, was not only identified by our screen, but has independently been implicated as an essential component of human pigmentation from a recent proteomic analysis of early melanosomes (Basrur, et al., 2002). Along with the recent release of the nearly complete zebrafish genome, these results suggest that nearly all genes implicated to date in vertebrate pigmentation are found in zebrafish and confirm the feasibility of using morpholinos for the investigation of pigmentation in this model vertebrate. As such, the zebrafish is uniquely positioned as a viable molecular genetic system for the study of conserved genes involved in vertebrate pigmentation.