Insertional mutagenesis and ear development

Human Genome Research

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Abstract

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 have been of particular interest. The first is a mutation in the forkhead related transcription factor Foxi1. This mutation has defects in both otic placode formation and jaw development. We are studying the mechanism of function for this transcription factor and are beginning to create a connection between sensory placode development and the formation of craniofacial elements. A second mutation that we are studying involves the disruption of a tight junction protein called claudinJ. Mutations in this gene cause deafness and vestibular defects in zebrafish embryos. We are trying to determine how this occurs. 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 retroviruse 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 process of mapping thousands of proviral integrations in the zebrafish germline to create an archived zebrafish mutant resource.