N-CAM binding inhibits the proliferation of hippocampal progenitor cells and promotes their differentiation to a neuronal phenotype

Cell adhesion molecules (CAMs) play important roles during the development of the nervous system. On the basis of our previous observations that bindi ng of the neural CAM (N-CAM) inhibits astrocyte proliferation and alters ge ne expression, we hypothesized that N-CAM may influence the balance between the proliferation and the differentiation of neural progenitor cells. Rat and mouse hippocampal progenitor cells were cultured and showed dependence on basic FGF for proliferation, immunoreactivity for nestin, the presence o f limited numbers of differentiated cells, and the ability to generate glia l cells and neurons under different culture conditions. Addition of soluble N-CAM reduced cell proliferation in a dose-dependent manner with no eviden ce of apoptosis. The inhibition of proliferation by N-CAM was accompanied b y an induction of differentiation to the neuronal lineage, as indicated by a twofold increase in the percentage of microtubule-associated protein 2-po sitive cells even in the presence of mitogenic growth factors. Experiments using hippocampal cells from N-CAM knock-out mice indicated that N-CAM on t he cell surface is not required for these effects, suggesting the existence of heterophilic signaling. These results support a role for N-CAM and N-CA M ligands in the inhibition of proliferation and the induction of neural di fferentiation of hippocampal neural progenitor cells.