Temporal patterning of neocortical progenitor cells: How do they know the right time?

During mammalian neocortical development, neural progenitor cells undergo sequential division to produce different types of progenies. Regulation of when and how many cells with a specific fate are produced from neural progenitor cells, i.e., 'temporal patterning' for cytogenesis, is crucial for the formation of the functional neocortex. Recently advanced techniques for transcriptome profiling at the single-cell level provide a solid basis to investigate the molecular nature underlying temporal patterning, including examining the necessity of cell-cycle progression. Evidence has indicated that cell-intrinsic programs and extrinsic cues coordinately regulate the timing of both the change in the division mode of neural progenitors from proliferative to neurogenic and their laminar fate transition from deep-layer to upper-layer neurons. Epigenetic modulation, transcriptional cascades, and post-transcriptional regulation are reported to function as cell-intrinsic programs, whereas extrinsic cues from the environment or surrounding cells supposedly function in a negative feedback or positive switching manner for temporal patterning. These findings suggest that neural progenitor cells have intrinsic temporal programs that can progress cell-autonomously and cell-cycle independently, while extrinsic cues play a critical role in tuning the temporal programs to let neural progenitor cells know the 'right' time to progress.