DOI: 10.5061/dryad.cv39v
title: Data from: The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation

description: We show that the splicing regulator PTBP2 controls a genetic program
 essential for neuronal maturation. Depletion of PTBP2 in developing mouse
 cortex leads to degeneration of these tissues over the first three
 postnatal weeks, a time when the normal cortex expands and develops mature
 circuits. Cultured Ptbp2−/− neurons exhibit the same initial viability as
 wild type, with proper neurite outgrowth and marker expression. However,
 these mutant cells subsequently fail to mature and die after a week in
 culture. Transcriptome-wide analyses identify many exons that share a
 pattern of mis-regulation in the mutant brains, where isoforms normally
 found in adults are precociously expressed in the developing embryo. These
 transcripts encode proteins affecting neurite growth, pre- and
 post-synaptic assembly, and synaptic transmission. Our results define a
 new genetic regulatory program, where PTBP2 acts to temporarily repress
 expression of adult protein isoforms until the final maturation of the
 neuron.
description: Li et al. Supplemental
 File 1: Table 1. Exons validated by RT/PCR.Table S1 for Li et al. A
 variety of exons showing differences in splicing between wild type and
 Ptbp2 nestin-KO brain at embryonic day 18 were subjected to further
 analysis by RT/PCR. These included exons identified by MJAY array, RNAseq,
 and exons previously reported to be PTBP targets. Gene names, exon
 coordinates, and percent spliced in values (PSI) are listed. Genome
 coordinates are for mm9.Supplemental File 1 Table S1
 RT-PCR validated E18 exons.docxLi et al. Supplemental
 File 2: Table 2. Splicing Changes Identified by Exon Junction
 Microarray.RNA from WT and
 Ptbp2-NestinKO E18 pups was analyzed on Affymetrix MJAY arrays (see
 Methods). Splicing events yielding Sepscores greater than 0.345 are
 listed.Supplemental File 2
 Table_S2_MJAY
 Array_top_Splicing_events_by_SepScore.xlsLi et al. Supplemental File 3: Table 3. Splicing Changes Identified by RNAseq analysis in Ptbp2-NesKO mice.RNAseq reads from E18 WT and NesKO mice were subjected to Splicetrap analysis (see Methods). Events with a change in PSI of greater than 10% are shown with genome coordinates, read numbers, and coverage statistics.Supplemental File 3 Table S3_nestin_nptbko_SpliceTrap_psi_over10percent_with_pvalues.xlsLi et al. Supplemental File 4: Table 4. Gene Ontology Analysis of Functional or Process Enrichment for Genes Showing Splicing Changes in Ptbp2-NesKO mice.Enrichments are relative to all genes expressed in wildtype brain at E18.Supplemental File 4 Table_S4_GO_analysis_nestin_splicetrap_exons.xlsLi et al. Supplemental File 5: Table 5. Expression changes in Ptbp2-NesKO mice.Genes showing overall expression changes were identified by Cuffdiff analysis.Supplemental File 5 Table_S5_cuffdiff_NesKOvWT_expression_change_V3.xlsLi et al. Supplemental File 6: Table 6. Gene Ontology analysis of genes up-regulated in Ptbp2-NesKO mice.Genes showing a two-fold or greater increase in expression in the KO relative to WT were analyzed for functional or process enrichment relative to all genes expressed in wildtype brain.Supplemental File 6 Table_S6_gene_ontology_2_fold_upregulated transcripts_v2.xlsLi et al. Supplemental File 7: Table 7. Gene Ontology analysis of genes down-regulated in Ptbp2-NesKO mice.Genes showing two-fold or greater reduced expression in the KO relative to WT were analyzed for functional or process enrichment relative to all genes expressed in wildtype brain.Supplemental File 7 Table_S7_gene_ontology_2_fold_change_down_regulated_transcripts_v2.xlsLi et al. Supplemental File 8: Table 8. Splicing Changes Identified by RNAseq analysis in Ptbp2-EmxKO mice.RNAseq reads from P1 WT and EmxKO mice were subjected to Splicetrap analysis (see Methods). Events with a change in PSI of greater than 10% are shown with genome coordinates, read numbers, and coverage statistics.Supplemental File 8 Table_S8_Emx_P1_SpliceTrap_psi_over10percent_with_pvalues.xls