Scaling and regeneration in the developing cerebellum

The cerebellum is a hindbrain structure that houses the majority of neurons in the mammalian brain and is involved in motor coordination, balance and higher cognitive processes. Compared to the rest of the brain, cerebellar development is protracted, with neurogenesis continuing postnatally. While the local circuitry of the cerebellum is relatively simple, having the correct proportions of its various cell types is essential for cerebellar function. Remarkably, the neonatal mouse cerebellum is highly regenerative upon injury at birth, utilizing context- and age-dependent regenerative strategies to ensure robust and efficient repair. Here, we provide an overview of how different lineages within the cerebellum interact during development and discuss the mechanisms of scaling, where the earlier-born neurons regulate the survival and proportional expansion of other cell types. We give examples of disorders where the scaling could be disrupted, perinatal injuries that affect the cerebellum and potential regenerative mechanisms in the brain. Furthermore, we discuss how the neonatal cerebellum regenerates the correct cell types in the appropriate proportions. Finally, we summarize the cell-intrinsic and -extrinsic mechanisms that regulate progenitor behaviors during postnatal cerebellar development and regeneration, specifically focusing on the nestin-expressing progenitors of the postnatal cerebellum.