Control of proliferation and differentiation of neural precursor cells: focusing on the developing cerebellum.

During CNS development, multipotent neural stem cells give rise first to various kinds of specified precursor cells, which proliferate extensively before terminally differentiating into either neurons or glial cells. Control of proliferation of the precursor cells plays a crucial role in determining the number of cells in the CNS. Proliferation is driven by mitogens, but how it is terminated remains a mystery. We examined the role of p27/Kip1 (p27), a cyclin-dependent kinase inhibitor, in the control of proliferation of cerebellar granule cell precursors (GCPs). We found that there is an intracellular mechanism that stops GCP division and causes GCPs to differentiate and that p27 is part of this mechanism. It is still not clear either whether the specified precursor cells are irreversibly determined to differentiate into their particular cell types. We examined the developmental plasticity of GCPs in vitro and found that at least some GCPs are not irreversibly committed to neuronal development but can be induced to differentiate into astroglial cells by appropriate extracellular signals.