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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Autores principales: Andreas Sagner, Isabel Zhang, Thomas Watson, Jorge Lazaro, Manuela Melchionda, James Briscoe
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Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/1f4bade4a91e47e8a61775cad7bde81e
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spelling oai:doaj.org-article:1f4bade4a91e47e8a61775cad7bde81e2021-12-02T19:54:42ZA shared transcriptional code orchestrates temporal patterning of the central nervous system.1544-91731545-788510.1371/journal.pbio.3001450https://doaj.org/article/1f4bade4a91e47e8a61775cad7bde81e2021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001450https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The 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.Andreas SagnerIsabel ZhangThomas WatsonJorge LazaroManuela MelchiondaJames BriscoePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 11, p e3001450 (2021)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Andreas Sagner
Isabel Zhang
Thomas Watson
Jorge Lazaro
Manuela Melchionda
James Briscoe
A shared transcriptional code orchestrates temporal patterning of the central nervous system.
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
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
title 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_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_sort shared transcriptional code orchestrates temporal patterning of the central nervous system.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/1f4bade4a91e47e8a61775cad7bde81e
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