Fig. 3: Loss of MYT1L disrupts excitatory neuron maturation at E14.

A UMAP of all E14 nuclei colored by pseudotime. B Box plots showing distributions of nuclei from excitatory neurons along pseudotime per genotype (n = 3 biological replicates per genotype: WT, Het, and KO). “#” indicates a significant difference between WT and Het distributions, and “#” indicates a significant difference between WT and KO distributions (FDR adjusted p < 0.05, two-sided Kolmogorov-Smirnov test). Box plots show median (center line), interquartile range (box), and whiskers extend to 1.5 times the interquartile range. C Representative plots showing the relative differences in distributions of MYT1L Het and KO nuclei compared to the WT distribution in the RG_2 and Im ExN_3 clusters. D Box plots showing the distributions of inhibitory neuron nuclei along pseudotime per genotype (n = 3 biological replicates per genotype: WT, Het, and KO). “#” indicates a significant difference between WT and Het distributions, and “*” indicates a significant difference between WT and KO distributions (FDR adjusted p < 0.05, two-sided Kolmogorov-Smirnov test). Box plots show median, interquartile range, and whiskers extending to 1.5 times the interquartile range. E Diagram displaying the breakdown of direct MYT1L targets identified by CUT&RUN that were transcription factors and showed gene expression changes across pseudotime in the excitatory neuron trajectory. F Heatmaps showing scaled expression of WT (left), Het (middle), and KO (right) excitatory neuron pseudotemporal genes. Each row represents a gene, with rows sorted according to their expression peak in pseudotime. Black tick marks on the right indicate rows where genes are MYT1L direct targets as determined by CUT&RUN in (E). G Scatterplot showing the Kullback-Liebler divergence metric used to identify differential pseudotemporal expression profiles in KOs compared to WT. H Representative traces of the differential pseudotemporal gene expression profiles for Tet2 and Hbp1 across genotypes.