Deciphering the roles of the RNA splicing machinery and axonal metabolism in the development of cortical circuits – SPLICEUP

Because they represent functional nodes of regulation for gene expression, RNA binding proteins are disproportionately associated to NeuroDevelopmental Disorders (NDDs) including Autism Spectrum Disorders (ASD). Understanding how these proteins may have cascading effect on core neuronal functions is critical to understand the pathophysiology of NDDs and propose therapeutic strategies. In light of recent studies demonstrating that autistic brains have altered patterns of gene expression and alternative mRNA splicing, we chose to study the neuronal functions of SON, a DNA/RNA binding protein and essential splicing factor whose mutation cause a rare neurodevelopmental and autism syndrome. Overall, our project will shed light on the crosstalk between mRNA regulation and cortical connectivity and provide mechanistic insight on how a deregulation of microexons, which are critical for neuronal development, can alter synaptic development and function in autistic syndromes.