Neural Cell Models of Specific Reading Disabilities: Identification of Cellular and Transcriptome Alterations

Based on post-mortem studies, a long-standing hypothesis on the biological bases of specific reading disabilities (RD) has been that alterations in neuronal migration alter language neural circuits. However, there are questions concerning the original studies (small sample size, comorbidities). Further, this idea has not been strongly supported by current genetic studies. In this study, we test altered neural cell phenotypes using cells derived from two pairs of siblings strongly discordant for reading-probands with severe RD and their strong-reader siblings. We observed significant differences in neurosphere outgrowth between the neural precursor cells (NPCs) from the probands compared to their strong-reader siblings. Transcriptome analyses of adherent NPCs and neurons derived from the NPCs identified genes differentially expressed between the probands and siblings, including genes previously identified in neurodevelopmental disorders. Of note was the overexpression of the hormone IGF1 and the transcription factor OTX2, responsible for the opening and closing of critical windows in development and predicted to be involved in critical windows for language acquisition. Our results support altered transcriptome and cellular phenotypes in RD neural cells and suggest possible molecular mechanisms underlying the changes.