SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE
The cerebellum is critical for motor coordination and cognitive function. Granule neurons are a key component of cerebellar circuitry and are thought to represent the cell of origin for the pediatric brain tumor medulloblastoma. Although the development of granule neurons has been studied in some detail, the signals that control their growth and differentiation remain unclear. During postnatal development, proliferation of granule neuron precursors (GNPs) is driven by the mitogen Sonic hedgehog (Shh), which is produced by neighboring Purkinje cells. However, GNPs also proliferate during embryonic development, at a stage prior to Shh secretion. Despite the importance of embryonic proliferation in establishing the pool of GNPs, the mitogen responsible for this proliferation is unknown. Our preliminary studies suggest that a mitogenic activity is present in extracts from the embryonic cerebellum, and we have proposed to identify the specific mitogen and study its role in cerebellar development.