Evolutionarily dynamic alternative splicing of GPR56 Regulates regional cerebral cortical patterning

Byoung Il Bae, Ian Tietjen, Kutay D. Atabay, Gilad D. Evrony, Matthew B. Johnson, Ebenezer Asare, Peter P. Wang, Ayako Y. Murayama, Kiho Im, Steven N. Lisgo, Lynne Overman, Nenad Sěstan, Bernard S. Chang, A. James Barkovich, P. Ellen Grant, Meral Topcu̧, Jeffrey Politsky, Hideyuki Okano, Xianhua Piao, Christopher A. Walsh

研究成果: Article査読

165 被引用数 (Scopus)


The human neocortex has numerous specialized functional areas whose formation is poorly understood. Here, we describe a 15-base pair deletion mutation in a regulatory element of GPR56 that selectively disrupts human cortex surrounding the Sylvian fissure bilaterally including "Broca's area," the primary language area, by disrupting regional GPR56 expression and blocking RFX transcription factor binding. GPR56 encodes a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor required for normal cortical development and is expressed in cortical progenitor cells. GPR56 expression levels regulate progenitor proliferation. GPR56 splice forms are highly variable between mice and humans, and the regulatory element of gyrencephalic mammals directs restricted lateral cortical expression. Our data reveal a mechanism by which control of GPR56 expression pattern by multiple alternative promoters can influence stem cell proliferation, gyral patterning, and, potentially, neocortex evolution.

出版ステータスPublished - 2014

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