Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536
Abstract Genetic variants in ZNF536 contribute to the risk for neuropsychiatric disorders such as schizophrenia, autism, and others. The role of this putative transcriptional repressor in brain development and function is, however, largely unknown. We generated znf536 knockout (KO) zebrafish and stu...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-024-02806-1 |
| _version_ | 1827326138683228160 |
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| author | Tae-Yoon Kim Arkaprava Roychaudhury Hyun-Taek Kim Tae-Ik Choi Seung Tae Baek Summer B. Thyme Cheol-Hee Kim |
| author_facet | Tae-Yoon Kim Arkaprava Roychaudhury Hyun-Taek Kim Tae-Ik Choi Seung Tae Baek Summer B. Thyme Cheol-Hee Kim |
| author_sort | Tae-Yoon Kim |
| collection | DOAJ |
| description | Abstract Genetic variants in ZNF536 contribute to the risk for neuropsychiatric disorders such as schizophrenia, autism, and others. The role of this putative transcriptional repressor in brain development and function is, however, largely unknown. We generated znf536 knockout (KO) zebrafish and studied their behavior, brain anatomy, and brain function. Larval KO zebrafish showed a reduced ability to compete for food, resulting in decreased total body length and size. This phenotype can be rescued by segregating the homozygous KO larvae from their wild-type and heterozygous siblings, enabling studies of adult homozygous KO animals. In adult KO zebrafish, we observed significant reductions in anxiety-like behavior and social interaction. These znf536 KO zebrafish have decreased cerebellar volume, corresponding to decreased populations of specific neuronal cells, especially in the valvular cerebelli (Va). Finally, using a Tg[mbp:mgfp] line, we identified a previously undetected myelin structure located bilaterally within the Va, which also displayed a reduction in volume and disorganization in KO zebrafish. These findings indicate an important role for ZNF536 in brain development and implicate the cerebellum in the pathophysiology of neuropsychiatric disorders. |
| first_indexed | 2024-03-07T14:40:18Z |
| format | Article |
| id | doaj.art-f1053d6566ff4c1db06ddfca4dea3737 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-07T14:40:18Z |
| publishDate | 2024-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-f1053d6566ff4c1db06ddfca4dea37372024-03-05T20:26:15ZengNature Publishing GroupTranslational Psychiatry2158-31882024-02-011411910.1038/s41398-024-02806-1Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536Tae-Yoon Kim0Arkaprava Roychaudhury1Hyun-Taek Kim2Tae-Ik Choi3Seung Tae Baek4Summer B. Thyme5Cheol-Hee Kim6Department of Biology, Chungnam National UniversityDepartment of Biology, Chungnam National UniversitySoonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang UniversityDepartment of Biology, Chungnam National UniversityDepartment of Life Sciences, Pohang University of Science and Technology (POSTECH)Department of Neurobiology, University of Alabama at BirminghamDepartment of Biology, Chungnam National UniversityAbstract Genetic variants in ZNF536 contribute to the risk for neuropsychiatric disorders such as schizophrenia, autism, and others. The role of this putative transcriptional repressor in brain development and function is, however, largely unknown. We generated znf536 knockout (KO) zebrafish and studied their behavior, brain anatomy, and brain function. Larval KO zebrafish showed a reduced ability to compete for food, resulting in decreased total body length and size. This phenotype can be rescued by segregating the homozygous KO larvae from their wild-type and heterozygous siblings, enabling studies of adult homozygous KO animals. In adult KO zebrafish, we observed significant reductions in anxiety-like behavior and social interaction. These znf536 KO zebrafish have decreased cerebellar volume, corresponding to decreased populations of specific neuronal cells, especially in the valvular cerebelli (Va). Finally, using a Tg[mbp:mgfp] line, we identified a previously undetected myelin structure located bilaterally within the Va, which also displayed a reduction in volume and disorganization in KO zebrafish. These findings indicate an important role for ZNF536 in brain development and implicate the cerebellum in the pathophysiology of neuropsychiatric disorders.https://doi.org/10.1038/s41398-024-02806-1 |
| spellingShingle | Tae-Yoon Kim Arkaprava Roychaudhury Hyun-Taek Kim Tae-Ik Choi Seung Tae Baek Summer B. Thyme Cheol-Hee Kim Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536 Translational Psychiatry |
| title | Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536 |
| title_full | Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536 |
| title_fullStr | Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536 |
| title_full_unstemmed | Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536 |
| title_short | Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536 |
| title_sort | impairments of cerebellar structure and function in a zebrafish ko of neuropsychiatric risk gene znf536 |
| url | https://doi.org/10.1038/s41398-024-02806-1 |
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