Cell-type-specific splicing of transcription regulators andPtbp1byRbfox1/2/3in the developing neocortex

Abstract

AbstractHow master splicing regulators crosstalk with each other and to what extent transcription regulators are differentially spliced remain unclear in the developing brain. Here, cell-type-specific RNA-Seq of the developing neocortex uncover that transcription regulators are enriched for differential splicing, altering protein isoforms or inducing nonsense-mediated mRNA decay. Transient expression of Rbfox proteins in radial glia progenitors induces neuronal splicing events preferentially in transcription regulators such asMeis2andTead1. Surprisingly, Rbfox proteins promote the inclusion of a mammal-specific alternative exon and a previously undescribed poison exon inPtbp1. Simultaneous ablation ofRbfox1/2/3in the neocortex downregulates neuronal isoforms and disrupts radial neuronal migration. Furthermore, the progenitor isoform ofMeis2promotesTgfb3transcription, while theMeis2neuron isoform promotes neuronal differentiation. These observations indicate that transcription regulators are differentially spliced between cell types in the developing neocortex.