Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-03-01
|
| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1009841 |
| _version_ | 1818319527628242944 |
|---|---|
| author | Fei Liu Yayun Qin Yuwen Huang Pan Gao Jingzhen Li Shanshan Yu Danna Jia Xiang Chen Yuexia Lv Jiayi Tu Kui Sun Yunqiao Han James Reilly Xinhua Shu Qunwei Lu Zhaohui Tang Chengqi Xu Daji Luo Mugen Liu |
| author_facet | Fei Liu Yayun Qin Yuwen Huang Pan Gao Jingzhen Li Shanshan Yu Danna Jia Xiang Chen Yuexia Lv Jiayi Tu Kui Sun Yunqiao Han James Reilly Xinhua Shu Qunwei Lu Zhaohui Tang Chengqi Xu Daji Luo Mugen Liu |
| author_sort | Fei Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T10:10:32Z |
| format | Article |
| id | doaj.art-5ec87f08a1f5433195e0b9eaee7ac910 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-13T10:10:32Z |
| publishDate | 2022-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-5ec87f08a1f5433195e0b9eaee7ac9102022-12-21T23:51:26ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-03-01183e100984110.1371/journal.pgen.1009841Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration.Fei LiuYayun QinYuwen HuangPan GaoJingzhen LiShanshan YuDanna JiaXiang ChenYuexia LvJiayi TuKui SunYunqiao HanJames ReillyXinhua ShuQunwei LuZhaohui TangChengqi XuDaji LuoMugen LiuNeural 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.https://doi.org/10.1371/journal.pgen.1009841 |
| spellingShingle | Fei Liu Yayun Qin Yuwen Huang Pan Gao Jingzhen Li Shanshan Yu Danna Jia Xiang Chen Yuexia Lv Jiayi Tu Kui Sun Yunqiao Han James Reilly Xinhua Shu Qunwei Lu Zhaohui Tang Chengqi Xu Daji Luo Mugen Liu Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration. PLoS Genetics |
| title | Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration. |
| title_full | Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration. |
| title_fullStr | Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration. |
| title_full_unstemmed | Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration. |
| title_short | Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration. |
| title_sort | rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration |
| url | https://doi.org/10.1371/journal.pgen.1009841 |
| work_keys_str_mv | AT feiliu rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT yayunqin rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT yuwenhuang rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT pangao rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT jingzhenli rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT shanshanyu rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT dannajia rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT xiangchen rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT yuexialv rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT jiayitu rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT kuisun rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT yunqiaohan rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT jamesreilly rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT xinhuashu rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT qunweilu rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT zhaohuitang rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT chengqixu rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT dajiluo rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration AT mugenliu rodgenesisdrivenbymafbainannrlknockoutzebrafishmodelwithalteredphotoreceptorcompositionandprogressiveretinaldegeneration |