The Francis Crick Institute
30343898.pdf (9.1 MB)

Nervous system regionalization entails axial allocation before neural differentiation

Download (9.1 MB)
journal contribution
posted on 2020-09-07, 11:09 authored by Vicki Metzis, Sebastian Steinhauser, Edvinas Pakanavicius, Mina Gouti, Despina Stamataki, Kenzo Ivanovitch, Thomas Watson, Teresa Rayon Alonso, S Neda Mousavy Gharavy, Robin Lovell-Badge, Nicholas M Luscombe, James Briscoe
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.