(Molecular Cell 2014, 56:90-103). A neural-specific splicing regulator previously discovered in the Blencowe laboratory, nSR100/SRRM4 (Calarco et al. Cell, 2009), activates this exon network by binding to adjacent, specialized intronic splicing enhancer motifs, and by facilitating the recruitment of multiple early splicing complex assembly factors. Discovery of this global splicing activation mechanism facilitates our understanding of the molecular mechanisms underlying neuronal differentiation, evolution for brain complexity, and neuronal developmental disorders such as autism.