<i>rad21</i> Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration
Previously, we identified RAD21<sup>R450C</sup> from a peripheral sclerocornea pedigree. Injection of this <i>rad21</i> variant mRNA into <i>Xenopus laevis</i> embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-medi...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/20/7807 |
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| author | Bi Ning Zhang Yu Liu Qichen Yang Pui Ying Leung Chengdong Wang Thomas Chi Bun Wong Clement C. Tham Sun On Chan Chi Pui Pang Li Jia Chen Job Dekker Hui Zhao Wai Kit Chu |
| author_facet | Bi Ning Zhang Yu Liu Qichen Yang Pui Ying Leung Chengdong Wang Thomas Chi Bun Wong Clement C. Tham Sun On Chan Chi Pui Pang Li Jia Chen Job Dekker Hui Zhao Wai Kit Chu |
| author_sort | Bi Ning Zhang |
| collection | DOAJ |
| description | Previously, we identified RAD21<sup>R450C</sup> from a peripheral sclerocornea pedigree. Injection of this <i>rad21</i> variant mRNA into <i>Xenopus laevis</i> embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea. Both gene expression and chromosome conformation of cell adhesion genes were affected in cells carrying the heterozygous <i>rad21</i> variant. Since cell migration is essential in early embryonic development and sclerocornea is a congenital disease, we studied neural crest migration during cornea development in <i>X. laevis</i> embryos. In <i>X. laevis</i> embryos injected with <i>rad21</i> mutant mRNA, neural crest migration was disrupted, and the number of neural crest-derived periocular mesenchymes decreased significantly in the corneal stroma region. Our data indicate that the RAD21<sup>R450C</sup> variant contributes to peripheral sclerocornea by modifying chromosome conformation and gene expression, therefore disturbing neural crest cell migration, which suggests RAD21 plays a key role in corneal stroma development. |
| first_indexed | 2024-03-10T15:26:53Z |
| format | Article |
| id | doaj.art-bed7ec074f9f4260a4a72ea8c1eb4967 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:26:53Z |
| publishDate | 2020-10-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bed7ec074f9f4260a4a72ea8c1eb49672023-11-20T18:02:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120780710.3390/ijms21207807<i>rad21</i> Is Involved in Corneal Stroma Development by Regulating Neural Crest MigrationBi Ning Zhang0Yu Liu1Qichen Yang2Pui Ying Leung3Chengdong Wang4Thomas Chi Bun Wong5Clement C. Tham6Sun On Chan7Chi Pui Pang8Li Jia Chen9Job Dekker10Hui Zhao11Wai Kit Chu12Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaProgram in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USADepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaProgram in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USAKey Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, ChinaDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaPreviously, we identified RAD21<sup>R450C</sup> from a peripheral sclerocornea pedigree. Injection of this <i>rad21</i> variant mRNA into <i>Xenopus laevis</i> embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea. Both gene expression and chromosome conformation of cell adhesion genes were affected in cells carrying the heterozygous <i>rad21</i> variant. Since cell migration is essential in early embryonic development and sclerocornea is a congenital disease, we studied neural crest migration during cornea development in <i>X. laevis</i> embryos. In <i>X. laevis</i> embryos injected with <i>rad21</i> mutant mRNA, neural crest migration was disrupted, and the number of neural crest-derived periocular mesenchymes decreased significantly in the corneal stroma region. Our data indicate that the RAD21<sup>R450C</sup> variant contributes to peripheral sclerocornea by modifying chromosome conformation and gene expression, therefore disturbing neural crest cell migration, which suggests RAD21 plays a key role in corneal stroma development.https://www.mdpi.com/1422-0067/21/20/7807<i>rad21</i>neural crest migration<i>Xenopus laevis</i>corneal stroma |
| spellingShingle | Bi Ning Zhang Yu Liu Qichen Yang Pui Ying Leung Chengdong Wang Thomas Chi Bun Wong Clement C. Tham Sun On Chan Chi Pui Pang Li Jia Chen Job Dekker Hui Zhao Wai Kit Chu <i>rad21</i> Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration International Journal of Molecular Sciences <i>rad21</i> neural crest migration <i>Xenopus laevis</i> corneal stroma |
| title | <i>rad21</i> Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration |
| title_full | <i>rad21</i> Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration |
| title_fullStr | <i>rad21</i> Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration |
| title_full_unstemmed | <i>rad21</i> Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration |
| title_short | <i>rad21</i> Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration |
| title_sort | i rad21 i is involved in corneal stroma development by regulating neural crest migration |
| topic | <i>rad21</i> neural crest migration <i>Xenopus laevis</i> corneal stroma |
| url | https://www.mdpi.com/1422-0067/21/20/7807 |
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