Direct cell-cell interactions control apoptosis and oligodendrocyte markerexpression of neuroepithelial cells

During brain development, the neuroepithelium generates neurons and glial c ells. Proliferation and differentiation of neuroepithelial cells are contro lled by a complex combination of secreted factors and more intrinsic or loc al mechanisms, such as lateral inhibition and asymmetric division. To obtai n further insights into the signals governing neuroepithelial cell fate, we used the immortomouse to derive conditionally immortalised cell lines from mouse E10 neuroepithelium. We isolated a nestin-positive basic fibroblast growth factor (bFGF)-responsive cell line (SVE10-23) which mostly different iate into astrocytes when cocultured with primary cortical cells. We found that, by simply lowering the cell density, SVE10-23 cells embarked on oligo dendrocytic differentiation as indicated by the strong expression of galact ocerebroside C and 2'3'-cyclic nucleotide 3'-phosphodiesterase. Apoptosis a ccompanied the differentiation, and all cells died within 1 week. We presen t here evidence that direct interactions between cells are the main mechani sm regulating this oligodendrocytic differentiation. We demonstrate that SV E10-23 cells contact or proximity inhibit their differentiation, prevent ap optosis, and promote their proliferation. Similarly, others nestin-positive precursor cell lines and nonimmortalised bFGF-grown E10 cells were found t o spontaneously differentiate at low density, thus generalising the idea th at neural precursor fate is regulated by direct cell-cell interactions. The SVE10-23 cell line provides a valuable tool with which to study further th e molecular components implicated in this mode of regulation. J. Neurosci. Res. 65:195-207, 2001. (C) 2001 Wiley-Liss, Inc.