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Regionalization of the nervous system requires axial allocation prior to neural lineage commitment

View ORCID ProfileVicki Metzis, View ORCID ProfileSebastian Steinhauser, Edvinas Pakanavicius, Mina Gouti, Despina Stamataki, Robin Lovell-Badge, Nicholas M Luscombe, View ORCID ProfileJames Briscoe
doi: https://doi.org/10.1101/229203
Vicki Metzis
1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
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  • ORCID record for Vicki Metzis
Sebastian Steinhauser
1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
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  • ORCID record for Sebastian Steinhauser
Edvinas Pakanavicius
1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
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Mina Gouti
1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
2Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10,Berlin 13092, Germany
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Despina Stamataki
1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
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Robin Lovell-Badge
1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
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Nicholas M Luscombe
1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
3UCL Genetics Institute, Department of Genetics Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK
4Okinawa Institute of Science & Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan
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James Briscoe
1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
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  • For correspondence: james.briscoe@crick.ac.uk
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Abstract

Summary Neural induction in vertebrates generates a central nervous system that extends the rostral-caudal length of the body. The prevailing view is that neural cells are initially induced with anterior (forebrain) identity, with caudalising signals then converting a proportion to posterior fates (spinal cord). To test this model, we used chromatin accessibility assays 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 central nervous system.

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Posted December 04, 2017.
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Regionalization of the nervous system requires axial allocation prior to neural lineage commitment
Vicki Metzis, Sebastian Steinhauser, Edvinas Pakanavicius, Mina Gouti, Despina Stamataki, Robin Lovell-Badge, Nicholas M Luscombe, James Briscoe
bioRxiv 229203; doi: https://doi.org/10.1101/229203
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Regionalization of the nervous system requires axial allocation prior to neural lineage commitment
Vicki Metzis, Sebastian Steinhauser, Edvinas Pakanavicius, Mina Gouti, Despina Stamataki, Robin Lovell-Badge, Nicholas M Luscombe, James Briscoe
bioRxiv 229203; doi: https://doi.org/10.1101/229203

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