Precursor cells in the subventricular zone of the adult mouse are activelyinhibited 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 precur sors, however, appear to be restricted in their capacity to generate neuron s in other regions of the brain indicating a tight regulation of their diff erentiation. We demonstrate in vitro that explants of SVZ are unable to gen erate 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, ind icating that bipotential precursors were present in the explants. Inhibitor y effects of cell density were more directly shown by plating freshly isola ted SVZ cells, or explant-derived SVZ cells, at increasing cell density. Th e frequency of neuron-containing wells was found to be greatly reduced at h igher cell concentrations: >100 cells/well in the case of explant-derived c ells 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 b y short-range factors. Copyright (C) 2000 S. Karger AG, Basel.