Nervous System Regionalization Entails Axial Allocation before Neural Differentiation

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, w...

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Veröffentlicht in:Cell Jg. 175; H. 4; S. 1105
Hauptverfasser: Metzis, Vicki, Steinhauser, Sebastian, Pakanavicius, Edvinas, Gouti, Mina, Stamataki, Despina, Ivanovitch, Kenzo, Watson, Thomas, Rayon, Teresa, Mousavy Gharavy, S Neda, Lovell-Badge, Robin, Luscombe, Nicholas M, Briscoe, James
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.11.2018
Schlagworte:
Animals
Cell Line
Cells, Cultured
Chick Embryo
Chromatin Assembly and Disassembly
Embryonic Induction
Female
Gene Expression Regulation, Developmental
Male
Mice
Mice, Inbred C57BL
Neural Stem Cells - cytology
Neural Stem Cells - metabolism
Neurogenesis
Spinal Cord - cytology
Spinal Cord - growth & development
Spinal Cord - metabolism
gene regulation
CDX
embryonic development
stem cells and development
computational genomics
spinal cord
chromatin
WNT signaling
ATAC-seq
neural induction
ISSN:1097-4172, 1097-4172
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2018.09.040