Fig. 5: Sensitivity of excitatory neurons persist throughout neurodevelopment to P21.

A UMAP projection showing 96,505 nuclei in 39 clusters from the cortex of P21 MYT1L WT (n = 6) and Het (n = 6) animals. B From left to right: summary plot showing the numbers of nuclei and genes detected in each cluster; bar plot displaying the mean ± SEM relative proportions of nuclei in each annotated cluster for MYT1L WT and Het genotypes; mean ± SEM proportions of Het normalized to WT; and number of differentially expressed genes (DEGs) per cell type upregulated in WT (light blue; n = 6 biological replicates) and upregulated in Het (blue; n = 6 biological replicates). Dot plots showing enriched GO biological processes terms in (C) MYT1L-activated (decreased expression in Het) and (D) MYT1L-repressed (increased expression in Het) DEGs. Overrepresentation of genes within GO terms was determined using a one-sided hypergeometric test, with p values adjusted for multiple testing using the Benjamini-Hochberg method. E, F Representative immunofluorescence images of brain sections from WT and MYT1L Het mice from a medial region (R2) and posterior (R3) region of the cortex. Upper panels show whole-brain sections stained for DARPP32 (green), NeuN (magenta), and DAPI (blue). Lower panels show higher magnification of the boxed areas in the upper panels, showing DARPP32 and NeuN staining separately. G Box plots showing quantification of DARPP32 and NeuN double-positive cell counts in three cortical regions (R1, R2, and R3) of WT and MYT1L Het mice. Each dot represents a counted section and is color-coded by animal. Box plots show median (center line), interquartile range (box), and whiskers extending to 1.5 times the interquartile range. Statistical significance was assessed using a linear mixed model comparison to test the effect of genotype while accounting for section differences and individual mouse variability. Significance is indicated by asterisks (***FDR adjusted p < 0.001, ANOVA).