TY - JOUR T1 - Precise temporal regulation of alternative splicing during neural development JF - bioRxiv DO - 10.1101/247601 SP - 247601 AU - Sebastien M. Weyn-Vanhentenryck AU - Huijuan Feng AU - Dmytro Ustianenko AU - Rachel Duffié AU - Qinghong Yan AU - Martin Jacko AU - Jose C. Martinez AU - Marianne Goodwin AU - Xuegong Zhang AU - Ulrich Hengst AU - Stavros Lomvardas AU - Maurice S. Swanson AU - Chaolin Zhang Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/01/14/247601.abstract N2 - Alternative splicing (AS) is a crucial step of gene expression that must be tightly controlled, but the precise timing of dynamic splicing switches during neural development and the underlying regulatory mechanisms are poorly understood. Here we systematically analyzed the temporal regulation of AS in a large number of transcriptome profiles of developing mouse cortices, in vivo purified neuronal subtypes, and neurons differentiated in vitro. Our analysis revealed early- and late-switch exons in genes with distinct functions, and these switches accurately define neuronal maturation stages. Integrative modeling suggests that these switches are under direct and combinatorial regulation by distinct sets of neuronal RNA-binding proteins including Nova, Rbfox, Mbnl and Ptbp. Surprisingly, various neuronal subtypes in the sensory systems lack Nova and/or Rbfox expression. These neurons retain the “immature” splicing program in early-switch exons, affecting numerous synaptic genes. These results provide new insights into the organization and regulation of the neurodevelopmental transcriptome. ER -