Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster
Abstract Neural stem and progenitor cell (NSPC) maintenance is essential for ensuring that organisms are born with proper brain volumes and head sizes. Microcephaly is a disorder in which babies are born with significantly smaller head sizes and cortical volumes. Mutations in subunits of the DNA org...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47042-9 |
| _version_ | 1797233496547131392 |
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| author | Bert I. Crawford Mary Jo Talley Joshua Russman James Riddle Sabrina Torres Troy Williams Michelle S. Longworth |
| author_facet | Bert I. Crawford Mary Jo Talley Joshua Russman James Riddle Sabrina Torres Troy Williams Michelle S. Longworth |
| author_sort | Bert I. Crawford |
| collection | DOAJ |
| description | Abstract Neural stem and progenitor cell (NSPC) maintenance is essential for ensuring that organisms are born with proper brain volumes and head sizes. Microcephaly is a disorder in which babies are born with significantly smaller head sizes and cortical volumes. Mutations in subunits of the DNA organizing complex condensin have been identified in microcephaly patients. However, the molecular mechanisms by which condensin insufficiency causes microcephaly remain elusive. We previously identified conserved roles for condensins in repression of retrotransposable elements (RTEs). Here, we show that condensin subunit knockdown in NSPCs of the Drosophila larval central brain increases RTE expression and mobility which causes cell death, and significantly decreases adult head sizes and brain volumes. These findings suggest that unrestricted RTE expression and activity may lead to improper brain development in condensin insufficient organisms, and lay the foundation for future exploration of causative roles for RTEs in other microcephaly models. |
| first_indexed | 2024-04-24T16:17:06Z |
| format | Article |
| id | doaj.art-e89e55165178416f950ff9afb9b489d5 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T16:17:06Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e89e55165178416f950ff9afb9b489d52024-03-31T11:24:25ZengNature PortfolioNature Communications2041-17232024-03-0115111510.1038/s41467-024-47042-9Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogasterBert I. Crawford0Mary Jo Talley1Joshua Russman2James Riddle3Sabrina Torres4Troy Williams5Michelle S. Longworth6Department of Inflammation and Immunity, Lerner Research Institute, Cleveland ClinicDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland ClinicDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland ClinicDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland ClinicDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland ClinicDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland ClinicDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland ClinicAbstract Neural stem and progenitor cell (NSPC) maintenance is essential for ensuring that organisms are born with proper brain volumes and head sizes. Microcephaly is a disorder in which babies are born with significantly smaller head sizes and cortical volumes. Mutations in subunits of the DNA organizing complex condensin have been identified in microcephaly patients. However, the molecular mechanisms by which condensin insufficiency causes microcephaly remain elusive. We previously identified conserved roles for condensins in repression of retrotransposable elements (RTEs). Here, we show that condensin subunit knockdown in NSPCs of the Drosophila larval central brain increases RTE expression and mobility which causes cell death, and significantly decreases adult head sizes and brain volumes. These findings suggest that unrestricted RTE expression and activity may lead to improper brain development in condensin insufficient organisms, and lay the foundation for future exploration of causative roles for RTEs in other microcephaly models.https://doi.org/10.1038/s41467-024-47042-9 |
| spellingShingle | Bert I. Crawford Mary Jo Talley Joshua Russman James Riddle Sabrina Torres Troy Williams Michelle S. Longworth Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster Nature Communications |
| title | Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster |
| title_full | Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster |
| title_fullStr | Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster |
| title_full_unstemmed | Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster |
| title_short | Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster |
| title_sort | condensin mediated restriction of retrotransposable elements facilitates brain development in drosophila melanogaster |
| url | https://doi.org/10.1038/s41467-024-47042-9 |
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