Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia
Abstract Retinal Müller glia have a capacity to regenerate neurons in lower vertebrates like zebrafish, but such ability is extremely limited in mammals. In zebrafish, Müller glia proliferate after injury, which promotes their neurogenic reprogramming while inhibiting reactive gliosis. In mammals, h...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50222-0 |
| _version_ | 1797377040137060352 |
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| author | Reiko Nishino Kaori Nomura-Komoike Tomohiro Iida Hiroki Fujieda |
| author_facet | Reiko Nishino Kaori Nomura-Komoike Tomohiro Iida Hiroki Fujieda |
| author_sort | Reiko Nishino |
| collection | DOAJ |
| description | Abstract Retinal Müller glia have a capacity to regenerate neurons in lower vertebrates like zebrafish, but such ability is extremely limited in mammals. In zebrafish, Müller glia proliferate after injury, which promotes their neurogenic reprogramming while inhibiting reactive gliosis. In mammals, however, how the cell cycle affects the fate of Müller glia after injury remains unclear. Here, we focused on the expression of proneural transcription factors, Ngn2 and Ascl1, and a gliosis marker glial fibrillary acidic protein (GFAP) in rat Müller glia after N-methyl-N-nitrosourea (MNU)-induced photoreceptor injury and analyzed the role of Müller glia proliferation in the regulation of their expression using retinal explant cultures. Thymidine-induced G1/S arrest of Müller glia proliferation significantly hampered the expression of Ascl1, Ngn2, and GFAP, and release from the arrest induced their upregulation. The migration of Müller glia nuclei into the outer nuclear layer was also shown to be cell cycle-dependent. These data suggest that, unlike the situation in zebrafish, cell cycle progression of Müller glia in mammals promotes both neurogenic reprogramming and reactive gliosis, which may be one of the mechanisms underlying the limited regenerative capacity of the mammalian retina. |
| first_indexed | 2024-03-08T19:48:15Z |
| format | Article |
| id | doaj.art-531a40b6e2d940e18bf11418e6136210 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T19:48:15Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-531a40b6e2d940e18bf11418e61362102023-12-24T12:14:07ZengNature PortfolioScientific Reports2045-23222023-12-0113111110.1038/s41598-023-50222-0Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller gliaReiko Nishino0Kaori Nomura-Komoike1Tomohiro Iida2Hiroki Fujieda3Department of Anatomy and Neurobiology, School of Medicine, Tokyo Women’s Medical UniversityDepartment of Anatomy and Neurobiology, School of Medicine, Tokyo Women’s Medical UniversityDepartment of Ophthalmology, School of Medicine, Tokyo Women’s Medical UniversityDepartment of Anatomy and Neurobiology, School of Medicine, Tokyo Women’s Medical UniversityAbstract Retinal Müller glia have a capacity to regenerate neurons in lower vertebrates like zebrafish, but such ability is extremely limited in mammals. In zebrafish, Müller glia proliferate after injury, which promotes their neurogenic reprogramming while inhibiting reactive gliosis. In mammals, however, how the cell cycle affects the fate of Müller glia after injury remains unclear. Here, we focused on the expression of proneural transcription factors, Ngn2 and Ascl1, and a gliosis marker glial fibrillary acidic protein (GFAP) in rat Müller glia after N-methyl-N-nitrosourea (MNU)-induced photoreceptor injury and analyzed the role of Müller glia proliferation in the regulation of their expression using retinal explant cultures. Thymidine-induced G1/S arrest of Müller glia proliferation significantly hampered the expression of Ascl1, Ngn2, and GFAP, and release from the arrest induced their upregulation. The migration of Müller glia nuclei into the outer nuclear layer was also shown to be cell cycle-dependent. These data suggest that, unlike the situation in zebrafish, cell cycle progression of Müller glia in mammals promotes both neurogenic reprogramming and reactive gliosis, which may be one of the mechanisms underlying the limited regenerative capacity of the mammalian retina.https://doi.org/10.1038/s41598-023-50222-0 |
| spellingShingle | Reiko Nishino Kaori Nomura-Komoike Tomohiro Iida Hiroki Fujieda Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia Scientific Reports |
| title | Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia |
| title_full | Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia |
| title_fullStr | Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia |
| title_full_unstemmed | Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia |
| title_short | Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia |
| title_sort | cell cycle dependent activation of proneural transcription factor expression and reactive gliosis in rat muller glia |
| url | https://doi.org/10.1038/s41598-023-50222-0 |
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