The neuronal migration hypothesis of dyslexia: a critical evaluation thirty years on

Guidi, Luiz G.; Velayos‐Baeza, Antonio; Martínez-Garay, Isabel; Monaco, Anthony P.; Paracchini, Silvia; Bishop, Dorothy V. M.; Molnár, Zoltán

doi:10.7287/peerj.preprints.26637

Cited by 3 publications

(6 citation statements)

References 12 publications

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“…Our study supports the emerging role for KIAA0319 in sensory organs adding to the debate around the different theories aimed at explaining the pathophysiology of developmental dyslexia. In particular, this study will contribute to the ongoing discussion around the role of neuronal migration in dyslexia (39), first proposed in the eighties and corroborated by the initial characterization of susceptibility genes, including KIAA0319.…”

Section: Discussionsupporting

confidence: 52%

“…The function of the KIAA0319 protein has been studied in human cell lines and in rodent models, however it has not been fully elucidated yet. The first functional characterization was conducted in rats and suggested a role in neuronal migration (11) while more recent studies in mouse indicated an involvement in biological processes beyond brain development (25,31,39).…”

Section: Kiaa0319-like Reported In Human Tissues (Supplementarymentioning

confidence: 99%

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

Gostić

Martinelli

Tucker

et al. 2018

Preprint

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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 otic vesicles, 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 higher and ubiquitous expression, was not expressed in the notochord suggesting a role specific to kiaa0319 in this structure. These data provide a framework to interpret the effects of the dyslexia-associated genetic variants that reside in the KIAA0319 regulatory sequences and might therefore affect a tightly regulated spatiotemporal expression pattern. This study contributes to our understanding of KIAA0319 function during embryonic development. In particular, our data support an emerging link with the auditory processing and propose additional roles in the visual system and in the notochord. 2

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Section: Discussionsupporting

confidence: 52%

Section: Kiaa0319-like Reported In Human Tissues (Supplementarymentioning

confidence: 99%

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

Gostić

Martinelli

Tucker

et al. 2018

Preprint

Self Cite

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“…Such anomalies are likely to be the result of neuronal migration defects. However, knockout mouse models for DYX1C1, DCDC2 and KIAA0319 did not exhibit cortical alterations [5], although heterotopias were observed in rats subjected to in utero knockdown of Dyx1c1 [6].…”

Section: Introductionmentioning

confidence: 92%

“…KIAA0319 encodes a transmembrane protein with five PKD domains [14,15] ( Figure 1A). Such structures have been previously found in cell surface proteins and are known to be involved in cell-cell and cell-matrix interactions [16] but the cellular function of KIAA0319 remains largely uncharacterised [5]. KIAA0319 has also been suggested to play a role in signalling pathways [17] and in axon growth inhibition [18].…”

Section: Introductionmentioning

confidence: 96%

“…The discordance between knockdown experiments in rat and knockout mouse models has been explained by species-specific effects, compensatory mechanisms in mice, or artefacts in shRNA experiments, and has been highlighted by recent reviews of the literature, providing interpretations either in support or raising doubts about the neuronal migration hypothesis [5,7,8].…”

Section: Introductionmentioning

confidence: 99%

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KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction

Diaz

Kronenberg

Martinelli

et al. 2019

Preprint

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Dyslexia is a common neurodevelopmental disorder with a strong genetic component. Independent genetic association studies have implicated the KIAA0319 gene in dyslexia, however its function is still unknown.We developed a cellular knockout model for KIAA0319 in RPE1 cells via CRISPR-Cas9n to investigate its role in processes suggested but not confirmed in previous studies, including cilia formation and cell migration.We found that KIAA0319 knockout increased cilia length and accelerated cell migration. Using Elastic Resonator Interference Stress Microscopy (ERISM), we detected an increase in cellular force for the knockout cells that was restored by a rescue experiment. Combining ERISM and immunostaining showed that KIAA0319 depletion reduced the number of podosomes formed by the cells.Our results suggest an involvement of KIAA0319 in mechanosensing and force regulation and shows for the first time that podosomes exert highly dynamic, piconewton vertical forces in epithelial cells.

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Beyond belongingness: Rethinking innate behavioral predispositions, learning constraints, and cognitive capacities

Sosa

2022

Adaptive Behavior

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Learning is a major determinant of behavioral change for some organisms through their lifecycles. From an associative perspective, learning is assumed to occur whenever organisms experience particular statistical regularities in their environment; specifically, meaningful outcomes that follow certain cues or actions chiefly contribute to behavioral change. However, numerous empirical reports reveal that not all cue–outcome and action–outcome combinations are learned equally well, a phenomenon that is termed belongingness. Those reports are valuable as descriptive-level knowledge, but beg further considerations, like what is the origin, adaptive value of, and underlying mechanisms associated with the predisposition to couple particular events. Contrary to what is often assumed, the mere observation of learning predispositions says little as to whether they arise from genetics, are constrained by hardwired neural circuitries, or have been ecologically advantageous in an evolutionary timescale. The present paper aims to present a number of notions from different research fields outside the hard core of associative learning and, in so doing, provides elements for careful study and conceptualization of this issue. Thereafter, these notions are pooled to understand behavioral variation in a wide array of phenomena, thus, bringing a more informed approach to the nature versus nurture debate.

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The neuronal migration hypothesis of dyslexia: a critical evaluation thirty years on

Abstract: 1The capacity for language is one of the key features underlying the complexity of human 2 cognition and its evolution. However, little is known about the neurobiological mechanisms that

Cited by 3 publications

References 12 publications

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

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

KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction

Beyond belongingness: Rethinking innate behavioral predispositions, learning constraints, and cognitive capacities

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