The cerebellum, relative to other brain structures, has a protracted developmental course, such that a considerable portion takes place postnatally. Its origins and those of its associated nuclei begin in week 7 of the embryonic period and its neurogenesis is complete some 6 months after birth. It starts in the embryonic period with neuroblasts located at the border of the fourth ventricle whose walls spread out laterally to form the rhombic lip at 5-6 weeks. This transient diamond-shaped cavity, which appears as a consequence of the pontine flexure (a bend in the long axis of the brain stem that subsequently disappears), gives rise to the cerebellum (a number of brain stem nuclei) that will eventually cover the fourth ventricle as it grows out more caudally than rostrally. More specifically, it is from a considerable increase in the size of the anterior rhombic lip that the cerebellum is formed (the posterior rhombic lip giving rise to the inferior olivary nucleus and its lateral corners to cochlear nuclei). The beginning of cerebellar development is also marked by the separation of the cortical plate from the intermediate zone. Neuroblasts remaining in this zone become the deep cerebellar nuclei, while those that migrate out from it become the Purkinje cells and Golgi type II inhibitory interneurons. The external granular layer is formed from the sub-ventricular zone at the edge of the rhombic lip. The axons of this layer, the last to develop in the cerebellum, grow parallel to each other, and thus are termed the parallel fibbers. At the same time, the granule cell bodies migrate inward along radial glial cells past the Purkinje cells to form the internal granular layer, and the Purkinje cell dendrites grow into the molecular layer where they then begin to branch profusely. Thus, unlike the cerebral cortex, the cerebellum undergoes an ‘outside-in’ pattern of migration (i.e., the granule cells migrate inward, possibly with the aid of pre-existing radial glial cells that act as guide wires as in the cerebral cortex, to form an new internal granular layer, and the Purkinje cells migrate radially outward). As for the Purkinje cells, each one synapses with the largest possible number of parallel fibers. The external granular layer is also the birthplace of the basket and stellate inhibitory interneurons, but which remain in the molecular layer. Neurons in the external granular layer continue cell division longer than most others in the developing brain. This layer still contains dividing cells at birth, with division (and proliferation) continuing until about 6 months after birth in the human. Thus, the external granule layer is the last to develop in the cerebellum, and as such has consequences for the development of movement coordination. PET scans, however, have revealed that cerebral glucose metabolism is higher in the cerebellum (as well as in sensorimotor cortex, thalamus and brain stem) compared to the basal ganglia and cerebral cortex at 5 weeks after birth, something that coincides quite well with the two-to-three month transformation resulting the first appearance of behaviour that appears to be under voluntary control. Furthermore, the later-occurring external granule cells are vulnerable not only to the effects of intrauterine growth restriction, but also to medulloblastoma, a malignant tumour occurring during this age range. If it remains restricted to the cerebellum, it may be possible to remove the tumour. This operation, however, entails ablating most of the cerebellum, and while the children who have had it can develop locomotion and postural control normally, they lose the ability for the motor learning required to acquire novel skills such riding a bicycle or skating. Other developmental disorders such as when the Purkinje cells are perturbed in their migration, result in a marked reduction of the number of granule cells that are essential in forming the regionalisation of the cerebellum. The converse is for some reason not the case. Postnatally, however, if the granular cell layer is adversely affected (e.g., through oxygen deprivation to which it is susceptible), then the Purkinje cells form dysmorpholgies such as disoriented and stunted dendritic spines. Thus, the interaction of the migrating Purkinje cells and granule cells is crucial to the formation of parallel fibers, the differentiation of the Purkinje cell dendritic trees, for synaptic contacts between them, and consequently for functional development more generally.
See Basal ganglia (development), Brain (neuro-) imaging, Brain stem, Cell migration, Cerebellum (anatomy), Cerebral cortex (development), Cerebellum (disorders), Cerebellum (functions), Coordination, Cortical lobes, Cortical plate, Dandy Walker malformation, Dendrite, Intrauterine growth restriction or retardation (IUGR), Medulloblastoma, Motor learning, Movement coordination, Neuroblasts, Neurogenesis, Neuronal migration disorders, Purkinje cells, Radial glia cells, Rhombic lip