It is generally assumed that neural stem cells give rise first to neuronal precursor cells, and that these precursor cells then proliferate extensively before terminally differentiating into postmitotic neurons. It is still not clear, however, whether the precursor cells are irreversibly determined to differentiate into neurons. In this study, we isolated immature cerebellar granule cell precursors from the developing mouse cerebellum. The immature precursors differentiated into granule cells in the absence of any signaling molecule, indicating that differentiation into neurons is the default pathway for these cells. A part of these immature neuronal precursors, however, differentiated into astrocytes when exposed to sonic hedgehog and bone morphogenetic proteins. Our results suggest that some, at least, neuronal precursor cells are not irreversibly committed to differentiating into neurons, but still have the plasticity to differentiate into astrocytes.

(Communicated by Tamio YAMAKAWA, M. J. A., Sept. 12, 2003)