A shared transcriptional code orchestrates temporal patterning of the central nervous system.
The molecular mechanisms that produce the full array of neuronal subtypes in the vertebrate nervous system are incompletely understood. Here, we provide evidence of a global temporal patterning program comprising sets of transcription factors that stratifies neurons based on the developmental time a...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-11-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001450&type=printable |
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| author | Andreas Sagner Isabel Zhang Thomas Watson Jorge Lazaro Manuela Melchionda James Briscoe |
| author_facet | Andreas Sagner Isabel Zhang Thomas Watson Jorge Lazaro Manuela Melchionda James Briscoe |
| author_sort | Andreas Sagner |
| collection | DOAJ |
| description | The molecular mechanisms that produce the full array of neuronal subtypes in the vertebrate nervous system are incompletely understood. Here, we provide evidence of a global temporal patterning program comprising sets of transcription factors that stratifies neurons based on the developmental time at which they are generated. This transcriptional code acts throughout the central nervous system, in parallel to spatial patterning, thereby increasing the diversity of neurons generated along the neuraxis. We further demonstrate that this temporal program operates in stem cell-derived neurons and is under the control of the TGFβ signaling pathway. Targeted perturbation of components of the temporal program, Nfia and Nfib, reveals their functional requirement for the generation of late-born neuronal subtypes. Together, our results provide evidence for the existence of a previously unappreciated global temporal transcriptional program of neuronal subtype identity and suggest that the integration of spatial and temporal patterning mechanisms diversifies and organizes neuronal subtypes in the vertebrate nervous system. |
| format | Article |
| id | doaj-art-1f4bade4a91e47e8a61775cad7bde81e |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2021-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-1f4bade4a91e47e8a61775cad7bde81e2025-08-20T03:25:34ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-11-011911e300145010.1371/journal.pbio.3001450A shared transcriptional code orchestrates temporal patterning of the central nervous system.Andreas SagnerIsabel ZhangThomas WatsonJorge LazaroManuela MelchiondaJames BriscoeThe molecular mechanisms that produce the full array of neuronal subtypes in the vertebrate nervous system are incompletely understood. Here, we provide evidence of a global temporal patterning program comprising sets of transcription factors that stratifies neurons based on the developmental time at which they are generated. This transcriptional code acts throughout the central nervous system, in parallel to spatial patterning, thereby increasing the diversity of neurons generated along the neuraxis. We further demonstrate that this temporal program operates in stem cell-derived neurons and is under the control of the TGFβ signaling pathway. Targeted perturbation of components of the temporal program, Nfia and Nfib, reveals their functional requirement for the generation of late-born neuronal subtypes. Together, our results provide evidence for the existence of a previously unappreciated global temporal transcriptional program of neuronal subtype identity and suggest that the integration of spatial and temporal patterning mechanisms diversifies and organizes neuronal subtypes in the vertebrate nervous system.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001450&type=printable |
| spellingShingle | Andreas Sagner Isabel Zhang Thomas Watson Jorge Lazaro Manuela Melchionda James Briscoe A shared transcriptional code orchestrates temporal patterning of the central nervous system. PLoS Biology |
| title | A shared transcriptional code orchestrates temporal patterning of the central nervous system. |
| title_full | A shared transcriptional code orchestrates temporal patterning of the central nervous system. |
| title_fullStr | A shared transcriptional code orchestrates temporal patterning of the central nervous system. |
| title_full_unstemmed | A shared transcriptional code orchestrates temporal patterning of the central nervous system. |
| title_short | A shared transcriptional code orchestrates temporal patterning of the central nervous system. |
| title_sort | shared transcriptional code orchestrates temporal patterning of the central nervous system |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001450&type=printable |
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