Development of cerebellar nuclei

Abstract

The cerebellum is a foliated structure consisting of the laminated cerebellar cortex and a paired set of bilateral cerebellar nuclei (CN) located in the deep white matter adjacent to the roof of the fourth ventricle. The CN are comprised of multiple neuron types including large glutamatergic projection neurons, GABAergic projection neurons, and small GABAergic interneurons. Hodologically, CN receive afferent projections from Purkinje cells, and give rise to major cerebellar output tracts. The developmental origins of CN have long been debated, although the consensus of evidence now indicates that different GABAergic (inhibitory) and glutamatergic (excitatory) neuronal populations are derived by sequential neurogenesis from distinct progenitor compartments. Each type of neuronal population is born at different times and follows a unique migratory route. The molecular mechanisms regulating CN neurogenesis, cellular migration, and axonal guidance of the efferent pathways are now being elucidated. This chapter highlights recent advances in embryonic cerebellar development, focusing on the development of CN and their connections, and on molecular mechanisms underlying their development. Mouse mutant phenotypes involving the CN, as well as human malformations affecting CN morphology, illustrate the importance of CN in cerebellar function and pathology.