Cerebellar histogenesis is disturbed in mice lacking cyclin D2

Formation of brain requires deftly balancing primary genesis of neurons and glia, detection of when sufficient cells of each type have been produced, shutdown of proliferation and removal of excess cells. The region and cell type-specific expression of cell cycle regulatory proteins, such as demonst rated for cyclin D2, may contribute to these processes. If so, regional bra in development should be affected by alteration of cyclin expression. To te st this hypothesis, the representation of specific cell types was examined in the cerebellum of animals lacking cyclin D2. The loss of this cyclin pri marily affected two neuronal populations: granule cell number was reduced a nd stellate interneurons were nearly absent, Differences between null and w ild-type siblings were obvious by the second postnatal week. Decreases in g ranule cell number arose from both reduction in primary neurogenesis and in crease in apoptosis of cells that fail to differentiate. The dearth of stel late cells in the molecular layer indicates that emergence of this subpopul ation requires cyclin D2 expression. Surprisingly, Golgi and basket interne urons, thought to originate from the same precursor pool as stellate cells, appear unaffected. These results suggest that cyclin D2 is required in cer ebellum not only for proliferation of the granule cell precursors but also for proper differentiation of granule and stellate interneurons.