Genome logic: the assignment of neural progenitor identity

V Metzis1, E Pakanavicius1, M Gouti1,2 and J Briscoe1

  1. The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom
  2. Max-Delbruck Center for Molecular Medicine, Berlin, Germany

In mammals, neural progenitors (NPs) derive from at least two lineages: the anterior neural tissue differentiates from the epiblast, while more posterior spinal cord arises from neuromesodermal progenitors (NMPs), the precursors of both paraxial mesoderm and spinal cord (SC). Whether these two routes towards neural progenitor fate specification are the result of distinct, or largely similar, neural induction mechanisms is unclear. Moreover, the timing and sequence of events that result in the assignment of neural identity, and to what extent other lineage choices must first be repressed remains to be resolved. To address these questions we are assessing genome-wide transcription factor binding and the resulting chromatin landscape in cells undergoing differentiation towards a NP fate with defined axial identities (anterior, hindbrain and posterior). Using methods we recently developed to direct the differentiation of mouse ESCs, we have mapped the genomic architecture of cells as they commit to a NP fate. Our data suggest that NPs possess a common set of regulatory regions that become accessible during neural differentiation. Overlaid with this signature, we have identified regulatory regions that appear to play a role in the establishment of anterior versus posterior neural progenitor fate. Our data suggest that chromatin accessibility plays a critical role in establishing lineage-specific cell states during the assignment of neural identity.