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Updated: Jan 1, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
Altered gene regulation as a candidate mechanism by which ciliopathy gene SDCCAG8 contributes to schizophrenia and
Mairéad Flynn1,2, Laura Whitton1, Gary Donohoe1
1Cognitive Genetics and Cognitive Therapy Group, Neuroimaging and Cognitive Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Ireland.
Abstract:
Mutations in genes that encode centrosomal/ciliary proteins cause severe cognitive deficits, while common single-nucleotide polymorphisms in these genes are associated with schizophrenia (SZ) and cognition in genome-wide association studies. The role of these genes in neuropsychiatric disorders is unknown. The ciliopathy gene SDCCAG8 is associated with SZ and educational attainment (EA). Genome editing of SDCCAG8 caused defects in primary ciliogenesis and cilium-dependent cell signalling. Transcriptomic analysis of SDCCAG8-deficient cells identified differentially expressed genes that are enriched in neurodevelopmental processes such as generation of neurons and synapse organization. These processes are enriched for genes associated with SZ, human intelligence (IQ) and EA. Phenotypic analysis of SDCCAG8-deficent neuronal cells revealed impaired migration and neuronal differentiation. These data implicate ciliary signalling in the aetiology of SZ and cognitive dysfunction. We found that centrosomal/ciliary genes are enriched for association with IQ, suggesting altered gene regulation as a general model for neurodevelopmental impacts of centrosomal/ciliary genes.
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