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

Abstract

Dyslexia is a common neurodevelopmental disorder caused by a significant genetic component. The KIAA0319 gene is one of the most robust dyslexia susceptibility factors 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 its zebrafish orthologue at different embryonic stages. We used different approaches including RNAscope in situ hybridization combined with light‐sheet microscopy. The results show particularly high expression during the first few hours of development. Later, expression becomes localized in well‐defined structures. In addition to high expression in the brain, we report for the first time expression in the eyes and the notochord. Surprisingly, kiaa0319‐like, which generally shows a similar expression pattern to kiaa0319, was not expressed in the notochord suggesting a distinct role for kiaa0319 in this structure. This observation was supported by the identification of notochord enhancers enriched upstream of the KIAA0319 transcription start site, in both zebrafish and humans. This study supports a developmental role for KIAA0319 in the brain as well as in other developing structures, particularly in the notochord which, is key for establishing body patterning in vertebrates.

Intramuscular Delivery of Gene Therapy for Targeting the Nervous System

“…Originally called KIAA0319L and linked with dyslexia and functions of neuronal migration and axon guidance (Poon et al, 2011), the AAV receptor (AAVR) possesses an N-terminal MANSC domain, several immunoglobulin-like PKD domains, a C6 domain, and a transmembrane region before a short C-terminal tail (Poon et al, 2011). As expected given the broad cellular and tissue infectivity of AAV, AAVR is expressed across many human tissues, including muscle and nerve, and can be found as several spliced variants and post-translationally modified isoforms (Poon et al, 2011;Gostic et al, 2019). AAVR knockout rendered mammalian HeLa cells highly resistant to infection with AAV serotypes 1, 2, 3b, 5, 6, 8, and 9, with a similar finding in AAV9-injected AAVR knockout mice in vivo (Pillay et al, 2016).…”

Developmental dyslexia genes are selectively targeted by diverse environmental pollutants

“…Our findings could be partially generalized to neurodevelopmental disorders, given that dyslexia risk genes are frequently expressed in the brain and contribute to brain development [ 58 ]. Based on gene expression data from the GTEx project across various tissues, dyslexia often involves susceptibility genes expressed throughout different regions of the brain [ 59 , 60 ] (Table S2 ). Dysregulation of these genes typically results in compromised brain development [ 61 ].…”

Cumulative genetic score of KIAA0319 affects reading ability in Chinese children: moderation by parental education and mediation by rapid automatized naming

“…Schmitz et al analyzed DNA methylation in the KIAA0319 promoter region to investigate whether epigenetic markers of language lateralization could be identified in nonneuronal tissue [ 7 ]. These data provide a framework to interpret the effects of the dyslexia-associated genetic variants that reside in KIAA0319 noncoding regulatory regions [ 8 ].…”