Chemical Regulation of Zebrafish Gene Expression

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Although the zebrafish has emerged as an ideal model of vertebrate biology, methods for evaluating zebrafish gene function remain underdeveloped. This application describes two interdisciplinary strategies for temporally and spatially controlling gene expression in zebrafish through chemical reagents. One method builds upon the zebrafish community's use of morpholino oligomers to selectively inhibit gene expression and involves the synthesis of caged morpholinos that become fluorescent upon their activation by light. The other approach uses ecdysone receptor agonists to induce transcriptional activation, with photoactivatable agonists providing additional spatial control. Both strategies will generate zebrafish with tailored gene expression patterns, providing new opportunities for understanding vertebrate physiology at the molecular and systems levels. Since zebrafish are used to study multiple aspects of vertebrate biology, these new experimental capabilities will advance our understanding of human development, physiology, and disease.