Insertional mutagenesis and ear development

Burgess, Shawn M.

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. Three of these mutations are being actively studied. 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 is in the zebrafish ortholog of the mouse gene Oct4. This gene is essential for maintaining stem cell pluripotency. We are performing transcriptional profiling in mouse ES cells and zebrafish embryos after modulating Oct4 levels. The third mutation affects the regenerative ability in several tissues of the zebrafish embryo including the hair cells of the inner ear. We are actively analyzing this mutation for its role in renewable cell populations. 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 process of mapping thousands of proviral integrations in the zebrafish germline to create an archived zebrafish mutant resource.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Human Genome Research Institute (NHGRI)
• Type: Intramural Research (Z01)
• Project #: 1Z01HG000183-04
• Application #: 6988859
• Study Section: (GTB)
• Support Year: 4
• Fiscal Year: 2004

Institution

• Name: Human Genome Research
• Country: United States

Publications

Liang, Jin; Burgess, Shawn M (2009) Gross and fine dissection of inner ear sensory epithelia in adult zebrafish (Danio rerio). J Vis Exp :

Gomez, Gustavo A; Veldman, Matthew B; Zhao, Yan et al. (2009) Discovery and characterization of novel vascular and hematopoietic genes downstream of etsrp in zebrafish. PLoS One 4:e4994

Jao, Li-En; Burgess, Shawn M (2009) Production of pseudotyped retrovirus and the generation of proviral transgenic zebrafish. Methods Mol Biol 546:13-30

Wang, Ting; Zeng, Jue; Lowe, Craig B et al. (2007) Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc Natl Acad Sci U S A 104:18613-8

Wang, Dongmei; Jao, Li-En; Zheng, Naizhong et al. (2007) Efficient genome-wide mutagenesis of zebrafish genes by retroviral insertions. Proc Natl Acad Sci U S A 104:12428-33

Ahmed, Zubair M; Goodyear, Richard; Riazuddin, Saima et al. (2006) The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15. J Neurosci 26:7022-34

Yan, Jizhou; Xu, Lisha; Crawford, Gregory et al. (2006) The forkhead transcription factor FoxI1 remains bound to condensed mitotic chromosomes and stably remodels chromatin structure. Mol Cell Biol 26:155-68

Wu, Xiaolin; Luke, Brian T; Burgess, Shawn M (2006) Redefining the common insertion site. Virology 344:292-5

Antonellis, Anthony; Lee-Lin, Shih-Queen; Wasterlain, Amy et al. (2006) Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons. J Neurosci 26:10397-406

Nakai, Hiroyuki; Wu, Xiaolin; Fuess, Sally et al. (2005) Large-scale molecular characterization of adeno-associated virus vector integration in mouse liver. J Virol 79:3606-14