PT  - JOURNAL ARTICLE
AU  - Weyn-Vanhentenryck, Sebastien M.
AU  - Feng, Huijuan
AU  - Ustianenko, Dmytro
AU  - Duffié, Rachel
AU  - Yan, Qinghong
AU  - Jacko, Martin
AU  - Martinez, Jose C.
AU  - Goodwin, Marianne
AU  - Zhang, Xuegong
AU  - Hengst, Ulrich
AU  - Lomvardas, Stavros
AU  - Swanson, Maurice S.
AU  - Zhang, Chaolin
TI  - Precise temporal regulation of alternative splicing during neural development
AID  - 10.1101/247601
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 247601
4099  - http://biorxiv.org/content/early/2018/01/14/247601.short
4100  - http://biorxiv.org/content/early/2018/01/14/247601.full
AB  - 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.