Displacement of M-phase nuclei in the ventricular zone of PS cDKO brains. (A-H) Phospho-histone 3 (p-histone 3, red) is used as a marker for cells in M-phase (A, B, E, F), whereas Tuj-1 (green) is used as an early neuronal marker (C, D, G, H). While the majority of the M-phase nuclei are found in the ventricular surface (closed arrowheads) of the control brain, many M-phase nuclei are found in basal are of the ventricular zone (opened arrowheads) in the developing cortical plate of PS cDKO brains at both E13.5 and E14.5, where strong Tuj-1-positive neuronal staining is observed. At E 14.5, most parts of the cortex are stained by Tuj-1 already in the mutant while clear layers are observed in the control. The pan early neuronal marker stained most area of the PS cDKO brain and only a very small part of the VZ are still left unstained (white star), suggesting that most of the neural progenitor cells are already being differentiated in the PS cDKO brain. The arrows indicate the meningeal cells. Scale bar: 100 μm. (I, J) Number and the location of p-histone 3 staining in the parasagital section of forebrain (750 μm width). At E13.5, in the sections the staining number is not different between the genotype. 76.0% ± 2.1% (SEM) of M-phase nuclei are detected in the VS (ventricular M phase nuclei) and about 24.0% of the M-phase nuclei were found in basal are of ventricular zone (non-ventricular M phase nuclei) in the control brain. 49.4% ± 3.6% of the M-phase staining in the PS cDKO brain are observed in the non-ventricular region, suggesting that the interkinetic nuclear migration is disrupted in the PS cDKO embryonic brain. n = 4 for each genotype (I). At E14.5, the p-histone 3 staining is much less in the PS cDKO embryos than control (p < 0.05). 20.1% ± 2.4% of the M-phase nuclei are detected in non ventricular position in the control, whereas 61.6% ± 4.9% of those are in non ventricular position in the PS cDKO ; n = 6 and 4 for the wild and mutant embryos respectively (J). (***, p < 0.001).