title: Developmental expression of the Nfe2-related factor (Nrf) transcription factor family in the zebrafish, Danio rerio.
abstract: Transcription factors in the CNC-bZIP family (NFE2, NRF1, NRF2 and NRF3) regulate genes with a wide range of functions in response to both physiological and exogenous signals, including those indicating changes in cellular redox status. Given their role in helping to maintain cellular homeostasis, it is imperative to understand the expression, regulation, and function of CNC-bZIP genes during embryonic development. We explored the expression and function of six nrf genes (nfe2, nrf1a, nrf1b, nrf2a, nrf2b, and nrf3) using zebrafish embryos as a model system. Analysis by microarray and quantitative RT-PCR showed that genes in the nrf family were expressed throughout development from oocytes to larvae. The spatial expression of nrf3 suggested a role in regulating the development of the brain, brachia and pectoral fins. Knock-down by morpholino anti-sense oligonucleotides suggested that none of the genes were necessary for embryonic viability, but nfe2 was required for proper cellular organization in the pneumatic duct and subsequent swim bladder function, as well as for proper formation of the otic vesicles. nrf genes were induced by the oxidant tert-butylhydroperoxide, and some of this response was regulated through family members Nrf2a and Nrf2b. Our results provide a foundation for understanding the role of nrf genes in normal development and in regulating the response to oxidative stress in vertebrate embryos.
authors.affiliation: Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts, United States of America ; Biology Department, Bates College, Lewiston, Maine, United States of America.
authors.forename: Larissa M
authors.initials: LM
authors.lastname: Williams
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Timme-Laragy
authors.forename: Jared V
authors.initials: JV
authors.lastname: Goldstone
authors.forename: Andrew G
authors.initials: AG
authors.lastname: McArthur
authors.forename: John J
authors.initials: JJ
authors.lastname: Stegeman
authors.forename: Roxanna M
authors.initials: RM
authors.lastname: Smolowitz
authors.forename: Mark E
authors.initials: ME
authors.lastname: Hahn
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics; D018384:Oxidative Stress; D014157:Transcription Factors / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D050984:NF-E2 Transcription Factor, p45 Subunit; D051267:NF-E2-Related Factor 2; C116462:NRF1 protein, zebrafish; D051266:Nuclear Respiratory Factor 1; D014157:Transcription Factors; D029961:Zebrafish Proteins; C494694:nfe2 protein, zebrafish; C495638:nfe2l2a protein, zebrafish; C000588906:nfe2l3 protein, zebrafish