Neuroblast-specific chromatin landscapes allow integration of spatial and temporal cues to generate neuronal diversity in Drosophila

Abstract

During early neurogenesis in flies and mice, spatial and temporal cues interact to specify neuronal diversity, yet in no organism is it known how spatial and temporal cues are integrated. We used Targeted DamID (TaDa) to identify the genomic binding sites of the temporal transcription factor Hunchback in two adjacent Drosophila neuroblasts (NB5-6 and NB7-4). Hunchback targets were different in each neuroblast. Profiling chromatin accessibility showed that each neuroblast had a distinct chromatin landscape: Hunchback-bound loci in NB5-6 were in open chromatin, but the same loci in NB7-4 were in closed chromatin. Moreover, binding of the spatial factor Gsb/Pax3, essential for NB5-6 specification, was correlated with open chromatin and Hunchback-enriched loci in NB5-6, but not NB7-4. We propose early-acting spatial factors establish a unique chromatin landscape in each neuroblast, thereby restricting temporal factor binding to different loci in each neuroblast, resulting in different neurons in each neuroblast lineage.\n\nImpact statementIntegration of spatial and temporal identity during Drosophila neurogenesis is due to spatial factors generating neuroblast-specific chromatin thereby biasing subsequent temporal transcription factor binding and producing neuroblast-specific neurons.