Knockdown of Kiaa0319 Reduces Dendritic Spine Density

Developmental Dyslexia is a reading disorder that affects individuals that possess otherwise normal intelligence. Until the four candidate dyslexia susceptibility genes were discovered, the cause of cortical malformations found in post mortem dyslexic brains was unclear. Normal brain development is crucial for the proper wiring of the neural circuitry that allow an individual to perform cognitive tasks like reading. For years, familial and twin studies have suggested that there was a genetic basis to the causation of dyslexia. Kiaa0319 was among the candidate dyslexia susceptibility genes that were ascertained. KIAA0319 is located on Chromosome 6p22.2-22.3 and has been found to exhibit differential spatial-temporal expression patterns in the brain throughout development, which suggests that the polycystic kidney disease (PKD) domain encoded by KIAA0319 facilitates cell-cell adhesion to enable neuronal precursors to crawl up the radial glia during neuronal migration. With the knowledge of KIAA0319 involvement in early neurogenesis, we were interested in determining how different KIAA0319 expression may impact cortical neurons in layer II and III during early adulthood. We show that KIAA0319 knockdown in cortical pyramidal neurons significantly reduces the dendritic spine density. Studies have shown that changes in dendritic spine morphology and density affect properties of neural circuitry. Henceforth, this finding may reveal a link between the Kiaa0319 gene and the deficit of the neural processing task of reading due to reduced spines density. Finding a correlation between Kiaa0319 expression and its influence on dendritic spine development may lead to a greater insight of a direct link between the dyslexia susceptibility gene and the biological mechanism that causes dyslexia.