The Developmental Genomics Section has been using a combination of zebrafish genetics and molecular embryology to study ear and hearing development. We have focused our attention on the study of several lines isolated in a screen for embryonically lethal mutations in zebrafish. Two of these mutations are being actively studied. The first is a mutation is in the zebrafish ortholog of the mouse gene Oct4. This gene is essential for maintaining stem cell pluripotency. We have performed transcriptional profiling in mouse ES cells and zebrafish embryos after modulating Oct4 levels. We are now in the process of perfoming ChIP-chip studies to establish the direct targets of Oct4 and their relationship to cell differentiation. The second mutation affects the regenerative ability in several tissues of the zebrafish embryo including the hair cells of the inner ear. We are cloning the transcript and establishing the subcellular localization of the protein and determining the function for the protein. Another focus of the lab is to develop tools for studying gene expression on a genome wide scale. We have developed a technique for rapidly mapping the integration sites for retroviruses and transposable elements and used that technique to define the global genomic profiles for MLV, HIV-1, and Sleeping Beauty based vectors. We are now in the second phase of a process to map thousands of proviral integrations in the zebrafish germline to create an archived zebrafish mutant resource. This phase will establish the framework for generating the resource and determine the number of total fish necessary to map 100,000 retroviral integrations.
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