Photochemical Regulation of Embryonic Gene Expression

描述(申请人提供)：尽管斑马鱼已经成为脊椎动物生物学的理想模型，但评估斑马鱼基因功能的方法仍然不发达。本申请描述了通过化学试剂在时间和空间上控制斑马鱼基因表达的两种跨学科策略。一种方法建立在斑马鱼群落使用吗啉低聚物选择性地抑制基因表达的基础上，涉及到笼子里的吗啉的合成，这些吗啉在被光激活后变得荧光。另一种方法使用蜕皮激素受体激动剂来诱导转录激活，而光激活激动剂则提供额外的空间控制。这两种策略都将产生具有定制基因表达模式的斑马鱼，为在分子和系统水平上理解脊椎动物生理学提供新的机会。由于斑马鱼被用来研究脊椎动物生物学的多个方面，这些新的实验能力将促进我们对人类发育、生理和疾病的理解。

DESCRIPTION (provided by applicant): 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.