Fig. 7: Q84Pfs-Het cortex showed a reduction of upper layer excitatory neurons and inhibitory interneurons and an increase of deep layer excitatory neurons.

The immunostaining analyses of Q84Pfs-Het and WT brains with cortical excitatory and inhibitory neuronal markers at E16 (a, b), P1 (c–e, j, k), P30 (f–i). BCL11B and TBR1 mark deep layer (DL) neurons, whereas CUX1 labels upper layer (UL) neurons. DLX1 marks cortical interneurons. a, b The yellow dotted lines indicate the upper limit of the cortical pyramidal neurons (a). BCL11B⁺ DL neurons increased, whereas UL neurons located above BCL11B⁺ neurons were markedly reduced in Q84Pfs-Het cortex at E16 (a, b). Similarly, the number of CUX1⁺ UL neurons, the thickness of CUX1⁺ UL, and the cortex thickness were significantly reduced in Q84Pfs-Het cortex at P1 (c–e) and P30 (f, g, h). The number of TBR1⁺ and BCL11B⁺ DL neurons increased, but the thickness of DL did not significantly change in Q84Pfs-Het cortex (c–h). The UL and DL were marked by yellow and magenta brackets, respectively (c, f). The number of DLX1⁺ interneurons was reduced in Q84Pfs-Het cortex (j,k). Scale bars, 100 μm (lower magnification images in a), 20 μm (higher magnification images in a), 500 μm (c, j), or 1 mm (f). n = 4 mice/condition for b, d, e, h, i, k; n = 7 mice/condition for g. The error bars represent SD. BCL11B: *p = 0.0243; CUX1: ****p < 0.0001 (b), DL: p = 0.8381; UL: ****p < 0.0001 (d), TBR1: *p = 0.0105; BCL11B: *p = 0.0126; CUX1: **p = 0.0029 (e), Cortex thickness: ****p < 0.0001 (g), UL thickness:***p = 0.0001 (h), DL thickness: p = 0.2130 (i), DLX1+ cells: **p = 0.0029 (k) in unpaired two-tailed t test. Only representative images are shown.