Figure 10

Models of Fas-mediated suicide sensitivity of precursors during cell cycle, and following disruption of cell-matrix interactions. Ventricular zone (VZ), interkinetic nuclear movement model: Our data shows that during cell cycle, cell-surface Fas expression is highest in neuroblasts that also exhibit the highest level of BrdU incorporation. Such a relationship would occur at the end of S-phase, perhaps reflecting DNA replication errors. Therefore, Fas expression (indicated in the cartoon by a green peri-cellular halo), and hence suicide-sensitivity would be highest during the ventricular-fugal interkinetic movement of nuclei transitioning through G2. Resident Fas-ligand expressing cells (indicated by pacman figures) could eliminate defective Fas-expressing neuroblasts. Cortical plate (CP), 'anoikis' model: Cortical neuroblasts utilize integrin-mediated signals to migrate along radial glia and into the laminae of the cortical plate [98]. Collagenase-A disrupts integrin-collagen interactions, and our data shows that collagenase-A leads to increased cell-surface Fas expression. Therefore, the induction of the Fas receptor may underlie the process of 'anoikis'. 'Anoikis' in turn, may protect the developing cerebral cortex from migration errors. Abbreviations: V = ventricular zone, VZ = ventricular zone, CP = cortical plate.