Abstract

With its limited diversity of neuronal types and stereotyped cellular organisation, the cerebellum is an excellent model for complex brain development. It exemplifies how simple patterning rules can give rise to complex neural circuits. The entirety of populations of excitatory and inhibitory neurons is characterised by the transient expression of either Atonal1 (Atoh1) or Ptf1a, respectively, and derived from a spatially defined population of Sox2-positive precursors. We present a model where the decision to make Atoh1 over Ptf1a lineage neurons is dictated by inductive cell-cell interactions at the posterior boundary with non-neural roof plate cells at the rhombic lip. The type of Atoh1+ve or Ptf1a+ve cell generated is dictated by a shared temporal code invested in the Sox2-expressing progenitor pool in the ventricular zone of dorsal rhombomere 1. An additional long-lived pool of Sox2 progenitors in the prospective white matter gives rise to glial cells (astrocytes) and later born interneurons, the latter of which also transiently express Ptf1a. Temporal patterning of progenitors generates neuronal diversity and offers a potent substrate for adaptation. In particular, fine-grained temporal patterning of progenitors feeding early rhombic lip derivatives dictates the connections of the cerebellum through specifying cerebellar nucleus output neurons which influence the scaling of the cortex of the cerebellum. In the human cerebellum, scaling involves species-specific adaptations that co-evolved within the human cerebral cortex.