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.
| Moore, John C; Sheppard-Tindell, Sarah; Shestopalov, Ilya A et al. (2013) Post-transcriptional mechanisms contribute to Etv2 repression during vascular development. Dev Biol 384:128-40 |
| Shestopalov, Ilya A; Pitt, Cameron L W; Chen, James K (2012) Spatiotemporal resolution of the Ntla transcriptome in axial mesoderm development. Nat Chem Biol 8:270-6 |
| Shestopalov, Ilya A; Chen, James K (2011) Spatiotemporal control of embryonic gene expression using caged morpholinos. Methods Cell Biol 104:151-72 |
| Shestopalov, Ilya A; Chen, James K (2010) Oligonucleotide-based tools for studying zebrafish development. Zebrafish 7:31-40 |
| Ouyang, Xiaohu; Chen, James K (2010) Synthetic strategies for studying embryonic development. Chem Biol 17:590-606 |
| Ouyang, Xiaohu; Shestopalov, Ilya A; Sinha, Surajit et al. (2009) Versatile synthesis and rational design of caged morpholinos. J Am Chem Soc 131:13255-69 |
| Chen, James K; Hurlstone, Adam F (2008) Targeted and Conditional Gene Expression Workshop, 8th International Conference on Zebrafish Development and Genetics. Zebrafish 5:193-195 |
| Shestopalov, Ilya A; Chen, James K (2008) Chemical technologies for probing embryonic development. Chem Soc Rev 37:1294-307 |
| Esengil, Hanife; Chen, James K (2008) Gene regulation technologies in zebrafish. Mol Biosyst 4:300-8 |
| Shestopalov, Ilya A; Sinha, Surajit; Chen, James K (2007) Light-controlled gene silencing in zebrafish embryos. Nat Chem Biol 3:650-1 |
Showing the most recent 10 out of 11 publications
