Figure 4.
Altered cortical neuronal distribution in Disc1 mutant mice. A, Cux1-labeled (top) and Brn2-labeled (bottom row) fluorescent images of WT, Q31L, and L100P (left to right) brains showed a slight shift of distribution of neurons toward deeper cortical layers in the mutants. B, Two equal ROIs across the cortex of both the Cux1-labeled and Brn2-labeled neurons were outlined. Each ROI was subdivided into eight equal octants in which the number of Cux1+ and Brn2+ cells were counted and expressed as a percentage of total cells in each ROI. A significantly higher proportion of Cux1+ cells was observed in WT (n = 62) than in both Q31L (n = 36) and L100P mutants (n = 44) in the first and third octant. Conversely, the proportion of Cux1+ cells in the fourth octant was significantly lower in WT than the two mutants (two-way ANOVA, t test, p < 0.01). C, Similarly, more Brn2+ cells were present in superficial cortical layers (octants 1 and 2) in WT than in mutants, while fewer Brn2+ cells were seen in deeper cortical layers (octants 4, 5, and 6) in WT (n = 52; two-way ANOVA, t test, p < 0.01). Together, these results indicate that more Cux1-labeled and Brn2-labeled cells are positioned in deeper cortical layers in Disc1 mutants vs WT. D, The distance from the deep edge of the Cux1 fluorescent neurons to the pia versus total cortical thickness within each ROI was also significantly higher in both mutants (t test, p < 0.01). Scale bar, 250 μm. All data are presented as mean ± SEM; *p < 0.05, **p < 0.01 versus WT. I–VI, Cortical layers I-VI.