Data from: The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation
Data files
Jan 14, 2015 version files 6.63 MB
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Supplemental File 1 Table S1 RT-PCR validated E18 exons.docx
44.28 KB
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Supplemental File 2 Table_S2_MJAY Array_top_Splicing_events_by_SepScore.xls
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Supplemental File 3 Table S3_nestin_nptbko_SpliceTrap_psi_over10percent_with_pvalues.xls
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Supplemental File 4 Table_S4_GO_analysis_nestin_splicetrap_exons.xls
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Supplemental File 5 Table_S5_cuffdiff_NesKOvWT_expression_change_V3.xls
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Supplemental File 6 Table_S6_gene_ontology_2_fold_upregulated transcripts_v2.xls
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Supplemental File 7 Table_S7_gene_ontology_2_fold_change_down_regulated_transcripts_v2.xls
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Supplemental File 8 Table_S8_Emx_P1_SpliceTrap_psi_over10percent_with_pvalues.xls
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Abstract
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.