FIGURE 3.

Possible mechanisms of spatiotemporal integration. (A) Direct cooperation: New regulators are introduced by an intrinsic cascade or by extrinsic signals and regulate target genes cooperatively with early regulators that are already present to establish distinct gene signatures for different neuronal types. (B) Epigenetic memory: Spatial and temporal factors might cooperate by early regulators establishing the chromatin landscape and defining a permissive subset of targets to be regulated by other regulators that are expressed later. The restriction of targets defines a specific set of post-mitotic regulators to be expressed after cell cycle exit. In ASE neurons, transient transcription in early development is sufficient to establish accessibility (Charest et al., 2020). (C) Regulator relay: When spatiotemporal factors are not co-expressed, the regulator that is expressed earlier might activate a downstream factor that is persistently expressed. When the later regulator is set to express, it directly cooperates with the downstream factor of the early regulator and activates a specific set of post-mitotic regulators. (t₁: first time-point, e.g., neural stem cell, t₂: second time-point, e.g., neuron).