The dyslexia susceptibility KIAA0319 gene shows a highly specific expression pattern during zebrafish development supporting a role beyond neuronal migration.

Abstract

Dyslexia is a common neurodevelopmental disorder that affects reading abilities and is predicted to be caused by a significant genetic component. Very few genetic susceptibility factors have been identified so far and amongst those, KIAA0319 is a key candidate. KIAA0319 is highly expressed during brain development but its function remains poorly understood. Initial RNA-interference studies in rats suggested a role in neuronal migration whereas subsequent work with double knock-out mouse models for both Kiaa0319 and its paralogue Kiaa0319-like reported effects in the auditory system but not in neuronal migration. To further understand the role of KIAA0319 during neurodevelopment, we carried out an expression study of the zebrafish orthologue at different embryonic stages. We report particularly high gene expression during the first few hours of development. At later stages, expression becomes localised in well-defined structures such as the eyes, the telencephalon and the notochord, supporting a role for kiaa0319 that is not restricted to brain development. Surprisingly, kiaa0319-like, which generally shows a similar expression pattern, was not expressed in the notochord suggesting a role specific to kiaa0319 in this structure. This study contributes to our understanding of KIAA0319 function during embryonic development which might involve additional roles in the visual system and in the notochord. Such a specific spatiotemporal expression pattern is likely to be under the controlled of tightly regulated sequences. Therefore, these data provide a framework to interpret the effects of the dyslexia-associated genetic variants that reside in KIAA0319 non-coding regulatory regions.