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Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration.
Liu, Fei; Qin, Yayun; Huang, Yuwen; Gao, Pan; Li, Jingzhen; Yu, Shanshan; Jia, Danna; Chen, Xiang; Lv, Yuexia; Tu, Jiayi; Sun, Kui; Han, Yunqiao; Reilly, James; Shu, Xinhua; Lu, Qunwei; Tang, Zhaohui; Xu, Chengqi; Luo, Daji; Liu, Mugen.
Afiliación
  • Liu F; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Qin Y; State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, The Innovative Academy of Seed Design, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan, P.R. China.
  • Huang Y; University of Chinese Academy of Sciences, Beijing, China.
  • Gao P; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Li J; Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Yu S; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Jia D; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Chen X; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Lv Y; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Tu J; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Sun K; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Han Y; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Reilly J; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Shu X; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Lu Q; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Tang Z; Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.
  • Xu C; Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.
  • Luo D; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • Liu M; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, P.R. China.
PLoS Genet ; 18(3): e1009841, 2022 03.
Article en En | MEDLINE | ID: mdl-35245286
ABSTRACT
Neural retina leucine zipper (NRL) is an essential gene for the fate determination and differentiation of the precursor cells into rod photoreceptors in mammals. Mutations in NRL are associated with the autosomal recessive enhanced S-cone syndrome and autosomal dominant retinitis pigmentosa. However, the exact role of Nrl in regulating the development and maintenance of photoreceptors in the zebrafish (Danio rerio), a popular animal model used for retinal degeneration and regeneration studies, has not been fully determined. In this study, we generated an nrl knockout zebrafish model via the CRISPR-Cas9 technology and observed a surprising phenotype characterized by a reduced number, but not the total loss, of rods and over-growth of green cones. We discovered two waves of rod genesis, nrl-dependent and -independent at the embryonic and post-embryonic stages, respectively, in zebrafish by monitoring the rod development. Through bulk and single-cell RNA sequencing, we characterized the gene expression profiles of the whole retina and each retinal cell type from the wild type and nrl knockout zebrafish. The over-growth of green cones and mis-expression of green-cone-specific genes in rods in nrl mutants suggested that there are rod/green-cone bipotent precursors, whose fate choice between rod versus green-cone is controlled by nrl. Besides, we identified the mafba gene as a novel regulator of the nrl-independent rod development, based on the cell-type-specific expression patterns and the retinal phenotype of nrl/mafba double-knockout zebrafish. Gene collinearity analysis revealed the evolutionary origin of mafba and suggested that the function of mafba in rod development is specific to modern fishes. Furthermore, the altered photoreceptor composition and abnormal gene expression in nrl mutants caused progressive retinal degeneration and subsequent regeneration. Accordingly, this study revealed a novel function of the mafba gene in rod development and established a working model for the developmental and regulatory mechanisms regarding the rod and green-cone photoreceptors in zebrafish.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Degeneración Retiniana / Pez Cebra Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2022 Tipo del documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Degeneración Retiniana / Pez Cebra Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2022 Tipo del documento: Article