Journal
CELL
Volume 175, Issue 4, Pages 1105-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2018.09.040
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Funding
- Francis Crick Institute
- Cancer Research UK [FC001051, FC0010110, FC001107]
- UK Medical Research Council [FC001051, FC0010110, FC001107]
- Wellcome [FC001051, FC0010110, FC001107, WT098326MA, 103760/Z/14/Z]
- BBSRC [BB/J015539/1]
- MRC [MR/L016311/1]
- NIH [R01-EB016629]
- Wellcome Trust [103760/Z/14/Z] Funding Source: Wellcome Trust
- BBSRC [BB/J015539/1] Funding Source: UKRI
- MRC [MR/L016311/1, MC_U117562207] Funding Source: UKRI
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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.
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