Fig. 4: Spatiotemporal differential gene expression analyses identifies dysregulation of cytoskeletal processes by Cul3 mutation.
a–c Differential gene expression analyses of cortical samples from embryonic (a), early postnatal (b), and adult (c) developmental periods. (Left panels) Volcano plots of differentially expressed genes in Cul3+/− vs WT. Genes colored in red are upregulated in Cul3+/− compared to WT; genes colored in blue are downregulated in Cul3+/− compared to WT; Cul3 is colored in pink. (Right panels) GO-terms enrichment of differentially expressed genes. Contribution of up- or downregulated genes to specific GO terms are shown in blue and red, respectively. d Heatmap of enriched common GO terms at different developmental time periods. Fisher P-value combination analysis (Materials and methods) was applied to identify 21 clusters of differentially expressed up- and downregulated genes impacted by Cul3 mutation across developmental periods. Biological processes impacted in two or more clusters are shown (Individual cluster details are present in Supplementary Table S6). e Enrichment of differentially expressed genes from each period and region with literature-curated gene lists with previous evidence for involvement in autism. These lists include pre- and post-synaptic genes from SynaptomeDB; syndromic and highly ranked (1 and 2) genes from SFARI Gene database (https://gene.sfari.org/database/gene-scoring/); genes with probability of loss-of-function intolerance (pLI) > 0.99 as reported by the Exome Aggregation Consortium; constrained genes; and FMRP target genes. Number of overlapped genes (in parenthesis) and odds ratio are indicated inside each cell, and provided only for FDR < 0.05 and OR > 1.
