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Nervous System Regionalization Entails Axial Allocation before Neural Differentiation

Metzis, V; Steinhauser, S; Pakanavicius, E; Gouti, M; Stamataki, D; Ivanovitch, K; Watson, T; ... Briscoe, J; + view all (2018) Nervous System Regionalization Entails Axial Allocation before Neural Differentiation. Cell , 175 (4) , Article e17. 10.1016/j.cell.2018.09.040. Green open access

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Abstract

Neural induction in vertebrates generates a CNS that extends the rostral-caudal length of the body. The prevailing view is that neural cells are initially induced with anterior (forebrain) identity; caudalizing signals then convert a proportion to posterior fates (spinal cord). To test this model, we used chromatin accessibility to define how cells adopt region-specific neural fates. Together with genetic and biochemical perturbations, this identified a developmental time window in which genome-wide chromatin-remodeling events preconfigure epiblast cells for neural induction. Contrary to the established model, this revealed that cells commit to a regional identity before acquiring neural identity. This "primary regionalization" allocates cells to anterior or posterior regions of the nervous system, explaining how cranial and spinal neurons are generated at appropriate axial positions. These findings prompt a revision to models of neural induction and support the proposed dual evolutionary origin of the vertebrate CNS.

Type: Article
Title: Nervous System Regionalization Entails Axial Allocation before Neural Differentiation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2018.09.040
Publisher version: http://doi.org/10.1016/j.cell.2018.09.040
Language: English
Additional information: Copyright 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: ATAC-seq, CDX, WNT signaling, chromatin, computational genomics, embryonic development, gene regulation, neural induction, spinal cord, stem cells and development
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/10060958
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