The neuronal migration hypothesis of dyslexia: A critical evaluation 30 years on

Abstract

The capacity for language is one of the key features underlying the complexity of human cognition and its evolution. However, little is known about the neurobiological mechanisms that mediate normal or impaired linguistic ability. For developmental dyslexia, early postmortem studies conducted in the 1980s linked the disorder to subtle defects in the migration of neurons in the developing neocortex. These early studies were reinforced by human genetic analyses that identified dyslexia susceptibility genes and subsequent evidence of their involvement in neuronal migration. In this review, we examine recent experimental evidence that does not support the link between dyslexia and neuronal migration. We critically evaluate gene function studies conducted in rodent models and draw attention to the lack of robust evidence from histopathological and imaging studies in humans. Our review suggests that the neuronal migration hypothesis of dyslexia should be reconsidered, and the neurobiological basis of dyslexia should be approached with a fresh start.

Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development

“…These include synaptic receptors, adhesion molecules, scaffolding proteins and cytoskeletal regulators. The molecular pathophysiology of dyslexia is less understood, but lines of evidence suggest that disruptions of neuronal migration and neurite outgrowth contribute importantly to the pathogenesis of the disease (Poelmans et al, 2011;Shao et al, 2016;Guidi et al, 2018). So far, very few shared risk genes have been identified in both ASD and dyslexia.…”

Dyslexia associated functional variants in Europeans are not associated with dyslexia in Chinese

“…DNAH9 encodes the heavy chain subunit of axonemal dynein that attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella (Bartoloni et al, ). Cilia movement has a role in guiding neuronal migration (Guidi et al, ; Higginbotham et al, ) and mutations in DNAH9 can cause respiratory defects (Fassad et al, ; Loges et al, ), which make DNAH9 a biologically plausible candidate. Besides, DNAH9 related super‐pathway “Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins” includes pathways regulating neuronal disorders such as Huntington disease (https://pathcards.genecards.org/Pathway/1260).…”

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

“…The function of the KIAA0319 protein has been studied in human cell lines and in rodent models, however it is not yet fully understood. The first functional characterization was conducted in rats and suggested a role in neuronal migration (Paracchini et al, ) while more recent studies in mice indicate an involvement in biological processes beyond brain development (Franquinho et al, ; Guidi et al, , ).…”

“…The first functional characterization was conducted in rats and suggested a role in neuronal migration (Paracchini et al, 2006) while more recent studies in mice indicate an involvement in biological processes beyond brain development (Franquinho et al, 2017;Guidi et al, 2017Guidi et al, , 2018.…”