The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube

The vertebrate neural tube generates a large diversity of molecularly and functionally distinct neurons and glia from a small progenitor pool. While the role of spatial patterning in organizing cell fate specification has been extensively studied, temporal patterning, which controls the timing of cell type generation, is equally important. Here, we define a global temporal program operating in progenitors throughout the mouse nervous systems that governs cell fate choices by controlling chromatin accessibility. Perturbation of this cis -regulatory program affects sequential cell fate transitions in neural progenitors and the identity of their progeny. The temporal program operates in parallel to spatial patterning, ensuring the timely availability of regulatory elements for spatial determinants to direct cell-type-specific gene expression. These findings identify a chronotopic spatiotemporal integration strategy in which a global temporal chromatin program determines the output of a spatial gene regulatory network resulting in the ordered allocation of cell type identity. • A temporal program of chromatin accessibility operates across CNS progenitors • This program integrates spatial inputs to direct cell-type-specific gene expression • A CRISPR screen identifies Nr6a1 and other regulators of the temporal program • Disrupting the temporal chromatin program affects neuronal subtype generation Zhang et al. identify a global temporal chromatin program that operates across the developing vertebrate nervous system to control neural cell diversity. This mechanism, which involves Nr6a1 and NFIA/B, integrates spatial and temporal patterning through sequential chromatin accessibility changes that direct when and where specific cell types are generated.