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KIAA0319 plays a critical role in cortical neuronal maturation and synaptic development through a dyslexia-associated gene network

ABSTRACT: Dyslexia is a common learning disorder defined as difficulty processing written language despite otherwise normal intelligence and access to adequate educational resources. To date, associations with reading performance have been replicated for nine genes, including KIAA0319. However, the specific role of KIAA0319 in the molecular mechanisms underlying dyslexia remains unclear. To investigate its function in neurodevelopment, we used CRISPR-Cas9 to generate KIAA0319 knockout (KIAA0319 -/-) human embryonic stem cells (hESCs), which were subsequently used to generate human cortical organoids (hCOs). Single-cell RNA sequencing revealed that KIAA0319 -/- neural progenitor cells favored a truncated radial glia (tRG) fate rather than a mature neuron fate. Transcriptomic analysis identified coordinated expression across multiple dyslexia-associated genes, suggesting that KIAA0319 operates within a broader regulatory network. This network was also implicated in regulating primary cilia formation, cortical organization, and synaptic connectivity, indicating that dyslexia-associated genes influence fundamental neurodevelopmental processes beyond their role in reading and language-related pathways.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303388 | GEO | 2025/12/17

REPOSITORIES: GEO

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