Precursor cells in the subventricular zone of the adult mouse are actively inhibited from differentiating into neurons.

The adult mouse subventricular zone (SVZ) contains precursor cells capable of generating new neurons which populate the olfactory bulb. The SVZ precursors, however, appear to be restricted in their capacity to generate neurons in other regions of the brain indicating a tight regulation of their differentiation. We demonstrate in vitro that explants of SVZ are unable to generate neurons from dividing precursors, even though precursors are present and dividing within explant cultures. However, when plated as single cells in fibroblast growth factor-1 or with no growth factor, approximately 1% of harvested cells gave rise to clones containing neurons and astrocytes, indicating that bipotential precursors were present in the explants. Inhibitory effects of cell density were more directly shown by plating freshly isolated SVZ cells, or explant-derived SVZ cells, at increasing cell density. The frequency of neuron-containing wells was found to be greatly reduced at higher cell concentrations: >100 cells/well in the case of explant-derived cells and >500 cells in the case of freshly isolated cells. Thus, it appears that the precursor's ability to generate neurons is actively inhibited by paracrine mechanisms which may be mediated by either cell-cell contact or by short-range factors.