Temporal trajectories underlying adult neuronal diversity

This review integrates longitudinal transcriptomic and functional studies to examine how embryonically born neurons acquire their adult identities. Single-cell atlases reveal that in addition to gene expression changes, neuron types undergo shifts in subtype composition as they mature from nascent to mature identities. Shifts in subtype composition likely reflect the unique sequence of developmental events followed by each neuron and explain why, in some neuron types, functional diversity in adults is not fully explained by adult transcriptomics alone. Instead, adult neuronal identity is best understood as a culmination of transient and stable transcriptomic changes over time that are regulated by the combinatorial action of sequentially activated intrinsic and extrinsic factors. Which factors regulate transcriptional transitions in each neuron type, how trajectories are coordinated across functionally related neurons, how chromatin states accommodate temporal changes, and whether time itself is an important factor in determining adult identity, remain open questions.