Specification of Granule Cells and Purkinje Cells

Granule cells and Purkinje cells are the major populations of neurons in the cerebellum. Their specification depends on a combination of regional identity and spatiotemporal cues. These are conferred by patterning systems in the early embryo that determine anteroposterior and dorsoventral positional coordinates and an age-dependent signal (or signals) whose nature is obscure. While a number of important questions remain about the nature of cerebellar progenitor pools and their precise boundaries, a variety of fate-mapping and genetic approaches have indicated that both granule cells and Purkinje cells arise from different dorsoventral domains within hindbrain rhombomere 1. Unusually, granule cell precursors undergo a subsequent transit amplification stage regulated by Purkinje cell signals, within a transient superficial germinal layer. Recent evolutionary insights suggest that this phase of Sonic hedgehog-dependent transit amplification is only found in amniotes. Evolutionarily, since secondary proliferation arose independently of granule cell specification, it is likely to be an adaptation purely for post-specification regulation of granule cell numbers.