Views on Four Key Questions About Zebrafish Research

Abstract

Our 2004 ‘‘Experts Speak’’ commentary included a series of well-considered perspectives on the potential contributions of the zebrafish to biology and human health. It is fun to look back on those comments. Since that time, the use of morpholino knockdowns as a reverse genetic tool has become commonplace. Insertional mutagenesis with evolving retroviral and now, transposon-based tools, has made it much easier to clone genes found in mutant screens, though the relative strength of ENU mutagenesis to detect phenotypically interesting mutations in essential genes remains. To challenge the ease of morpholino knock-downs in zebrafish, somatic cell knockdowns of mammalian cell culture cells with RNAi has now become commonplace. Broadly-applicable targeted engineering of animal genomes, including zebrafish, looms tantalizingly on the horizon. Before Steve Ekker0s arrival as our new editor, to take another ‘‘snap shot’’ of our moving field, I was asked to help find out what some senior members of the zebrafish community think aboutwhereweare, focusing on four questions (and a ‘‘grab bag’’of questions). Most striking was the large increase in discussion of relevance of the zebrafish to humans, which validates past and future NIH support for zebrafish research. The answers we received are presented in alphabetical order by investigator last name, with editorial changes in brackets. May these comments inspire an everclearer vision of how the zebrafish will contribute to our understanding of the living world.