The cerebellum is critical for motor coordination and cognitive function and is the target of transformation in medulloblastoma, the most common malignant brain tumor in children. Although the development of granule cells, the most abundant neurons in the cerebellum, has been studied in detail, the origins of other cerebellar neurons and glia remain poorly understood. Here we show that the murine postnatal cerebellum contains multipotent neural stem cells (NSCs). These cells can be prospectively isolated based on their expression of the NSC marker prominin-1 (CD133) and their lack of markers of neuronal and glial lineages (lin -). Purified prominin + lin -cells form self-renewing neurospheres and can differentiate into astrocytes, oligodendrocytes and neurons in vitro. Moreover, they can generate each of these lineages after transplantation into the cerebellum. Identification of cerebellar stem cells has important implications for the understanding of cerebellar development and the origins of medulloblastoma.The cerebellum is required for motor coordination and is crucial for cognitive and affective processing 1 . These functions depend on interactions among at least six types of neurons and two types of glia 2 . Disruption of cerebellar structure and function is associated with disorders such as ataxia, autism and schizophrenia 3-5 . In addition, uncontrolled growth of cerebellar precursors results in medulloblastoma 6,7 . Elucidating the mechanisms that control the generation of cerebellar neurons and glia during normal development is critical for understanding the basis of these diseases.The cerebellum differs from most other brain regions in that it contains two distinct germinal layers: the ventricular zone (VZ), which is most active during embryonic development, and the external germinal layer (EGL), which contributes to neurogenesis after birth 2 . There is strong evidence that Purkinje cells, the major output neurons of the cerebellum, originate from the VZ and that granule cells, the most abundant interneurons, arise from the EGL. However, the origin of the other cell types in the cerebellar cortex-including astrocytes, oligodendrocytes and stellate, basket, Lugaro and Golgi interneurons-is much less clear. Tissue grafting and transplantation studies suggest that many of these cells arise from VZ progenitors that migrate into the cerebellar cortex after birth 8,9 . But whether each class of neuron and glial cell comes from a distinct progenitor or whether they all come from a common, multipotent progenitor is not known. Here we purify a population of multipotent neural stem cells from the postnatal cerebellum. We show that this population can undergo self-renewal in culture and can generate neurons, astrocytes and oligodendrocytes both in vitro and after transplantation. Our findings suggest that cerebellar neurons and glia could be generated from a common progenitor. In addition, the approach we have used may be applicable for isolating NSCs from other parts of the nervous system. RESULTS Non-g...

neuron ͉ cerebellum ͉ granule cell