A shared transcriptional code orchestrates temporal patterning of the central nervous system
Open Access
- 12 November 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Biology
- Vol. 19 (11), e3001450
- https://doi.org/10.1371/journal.pbio.3001450
Abstract
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.Funding Information
- Cancer Research UK (FC001051)
- Medical Research Council (FC001051)
- Wellcome Trust (FC001051)
- H2020 European Research Council (742138)
- Human Frontier Science Program (LTF000401/2014-L)
- University of Manchester (Presidential Fellowship)
- Deutsche Forschungsgemeinschaft (455354162)
- Cancer Research UK (C157/A23459)
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