Abstract

The goal of the work proposed is the establishment of technologies and resources that will facilitate the genetic analysis of vertebrate development using zebrafish. The zebrafish is an attractive, easily accessible animal model to study the genetics of embryogenesis. Already, chemical mutagenesis screens have generated more than one thousand mutants that have defects in most developmental processes. This proposal consists of three parts. The first part describes the generation of balancer chromosomes with a transgene marker that will facilitate identification of zebrafish mutants. The second part describes the development of transgenic technology using yeast and bacterial artificial chromosomes in the zebrafish. This technology will be useful for identifying the chemically induced mutant genes after they have been mapped to specific chromosomal loci. In addition, artificial chromosomes can be used to study the regulation of gene expression by allowing one to identify cis-acting regulatory regions that lie many kilobases away from a gene's transcription initiation site. The third part describes the generation of transgenic zebrafish lines that express the green fluorescent reporter gene in each of the major tissues including the notochord, the nervous system, the brain, heart, and others. These transgenic fish will be available for use by anyone in the zebrafish community.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR013227-06
Application #
6640660
Study Section
Genome Study Section (GNM)
Program Officer
Chang, Michael
Project Start
1999-01-15
Project End
2004-09-19
Budget Start
2003-01-15
Budget End
2004-09-19
Support Year
6
Fiscal Year
2003
Total Cost
$289,236
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Tehrani, Zahra; Lin, Shuo (2011) Antagonistic interactions of hedgehog, Bmp and retinoic acid signals control zebrafish endocrine pancreas development. Development 138:631-40
Liu, Ning-Ai; Jiang, Hong; Ben-Shlomo, Anat et al. (2011) Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor. Proc Natl Acad Sci U S A 108:8414-9
Ríos, Yesenia; Melmed, Shlomo; Lin, Shuo et al. (2011) Zebrafish usp39 mutation leads to rb1 mRNA splicing defect and pituitary lineage expansion. PLoS Genet 7:e1001271
Qi, Fei; Song, Jianbo; Yang, Hanshuo et al. (2010) Mmp23b promotes liver development and hepatocyte proliferation through the tumor necrosis factor pathway in zebrafish. Hepatology 52:2158-66
Jiang, Zhi; Song, Jianbo; Qi, Fei et al. (2008) Exdpf is a key regulator of exocrine pancreas development controlled by retinoic acid and ptf1a in zebrafish. PLoS Biol 6:e293
Song, Jianbo; Kim, Hyon J; Gong, Zhiyuan et al. (2007) Vhnf1 acts downstream of Bmp, Fgf, and RA signals to regulate endocrine beta cell development in zebrafish. Dev Biol 303:561-75
Ju, Bensheng; Huang, Haigen; Lee, Ki-Young et al. (2004) Cloning zebrafish by nuclear transfer. Methods Cell Biol 77:403-11
Penberthy, William Todd; Zhao, Chengtian; Zhang, Yu et al. (2004) Pur alpha and Sp8 as opposing regulators of neural gata2 expression. Dev Biol 275:225-34
Liu, Ning-Ai; Huang, Haigen; Yang, Zhongan et al. (2003) Pituitary corticotroph ontogeny and regulation in transgenic zebrafish. Mol Endocrinol 17:959-66
Young, Rodrigo M; Marty, Scott; Nakano, Yoshiro et al. (2002) Zebrafish yolk-specific not really started (nrs) gene is a vertebrate homolog of the Drosophila spinster gene and is essential for embryogenesis. Dev Dyn 223:298-305

Showing the most recent 10 out of 15 publications