Fig. 1.

Modular organization of dynamic splicing switches during cortex development. a The number of non-redundant cassette exons with differential splicing (|ΔΨ| ≥ 0.2, Benjamini FDR ≤ 0.05) in each pairwise comparison of developmental stages. The numbers of exons with increased inclusion at later stages are shown above the diagonal (top right), and exons with decreased inclusion at later stages are shown below the diagonal (bottom left). b Mouse cassette exons with developmental changes are highly conserved in human, as measured by the percentage of exons with conserved splicing in human (left) or the percentage of exons under strong evolutionary selection pressure (right). c An example of developmental splicing regulation in exon 8a of the Kdm1a gene. Inclusion of this microexon peaks between postnatal days P0–P7. d Four modules of developmentally regulated exons identified by WGCNA analysis with distinct temporal patterns during cortex development. A non-redundant set of 2883 known and novel cassette exons was included for this analysis, and their mean-substracted inclusion levels across developmental stages are shown in the heatmap. Exons in each module were ranked based on their correlation with the eigenvector of the module, and those with the strongest correlation are defined as core members (black bars on the right). Exons in each module are further divided into two groups (e.g., M1+ and M1−) depending on positive or negative correlation with the eigenvector. e Enrichment of gene ontology (GO) terms in exons showing splicing switches with specific timing. The timing of developmental splicing switches is parameterized by sigmoidal curve fitting, and exons are ranked based on the timing. Exons in each sliding window (with a window size of 300 exons) were compared to all cassette exons with sufficient read coverage in the brain to identify significant GO terms. Only GO terms significant in at least one sliding window are shown (Benjamini FDR ≤0.05). Broad categories and top GO terms in each category are highlighted on the right