Gal4 Driver Transgenic Zebrafish: Powerful Tools to Study Developmental Biology, Organogenesis, and Neuroscience

Targeted expression by the Gal4-UAS system is a powerful genetic method to analyze the functions of genes and cells in vivo. Although the Gal4-UAS system has been extensively used in genetic studies in Drosophila, it had not been applied to genetic studies in vertebrates until the mid-2000s. This was mainly due to the lack of an efficient transgenesis tool in model vertebrates, such as the P-transposable element of Drosophila, that can create hundreds or thousands of transgene insertions in different loci on the genome and thereby enables the generation of transgenic lines expressing Gal4 in various tissues and cells via enhancer trapping. This situation was revolutionized when a highly efficient transgenesis method using the Tol2 transposable element was developed in the model vertebrate zebrafish. By using the Tol2 transposon system, we and other labs successfully performed gene trap and enhancer trap screens in combination with the Gal4-UAS system. To date, numerous transgenic fish lines that express engineered versions of Gal4 in specific cells, organs, and tissues have been generated and used for various aspects of biological studies. By constructing transgenic fish lines harboring genes of interest downstream of UAS, the Gal4-expressing cells and tissues in those transgenic fish have been visualized and manipulated via the Gal4-UAS system. In this review, we describe how the Gal4-UAS system works in zebrafish and how transgenic zebrafish that express Gal4 in specific cells, tissues, and organs have been used for the study of developmental biology, organogenesis, and neuroscience.