Investigating developmental and disease mechanisms of the cerebellum with pluripotent stem cells

The cerebellum is a brain region located in the dorsal part of the anterior hindbrain, composed of a highly stereotyped neural circuit structure with small sets of neurons. The cerebellum is involved in a wide variety of functions such as motor control, learning, cognition and others. Damage to the cerebellum often leads to impairments in motor skills (cerebellar ataxia). Cerebellar ataxia can occur as a result of neurodegenerative diseases such as spinocerebellar ataxia. Recent advances in technologies related to pluripotent stem cells and their neural differentiation has enabled researchers to investigate the mechanisms of development and of disease in the human brain. Here, we review recent applications of leading-edge stem cell technologies to the mechanistic investigation of human cerebellar development and neurological diseases affecting the cerebellum. •Developmental mechanisms of the cerebellum have been revealed in model animals.•3D self-organizing culture of PSCs recapitulates cerebellar tissue formation.•PSC-derived cerebellum can be used for mechanistic study of human cerebellum.•Spinocerebellar ataxia (SCA) is a disease with neurodegeneration of the cerebellum.•SCA patient iPSC-derived cerebellum enables pathological study and drug screening.