Principles of Brain Region Evolution: Insights from the Cerebellar Nuclei

How do new brain regions evolve? The cerebellar nuclei, the output structures of the cerebellum, are an ideal model for studying this question due to their striking diversification across vertebrates: Mammals have three bilaterally symmetric nuclei, birds and reptiles have two, and amphibians and cartilaginous fishes have one. Here, we review comparative, developmental, and transcriptomic data on the evolution of the cerebellar nuclei. We propose that the repeated duplication of a conserved cell type set coupled with excitatory neuron divergence underlies cerebellar nucleus diversification. We also discuss the possible origins of the ancestral cerebellar nucleus, likely through a duplication-and-divergence event of extracerebellar hindbrain structures. Finally, we explore how similar duplication-and-divergence mechanisms operate in other brain regions, underscoring this mechanism as a general principle governing the emergence of new brain structures.