Neural Cell Models of Specific Reading Disabilities: Identification of Migration 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, this idea has not been strongly supported by current genetic studies. In this study, we test neural cell migration using cells derived from two pairs of siblings strongly discordant for reading – probands with severe RD and their strong readers siblings. We observed significant differences in migration in the neurosphere assay with the neural precursor cells (NPCs) from the probands migrating significantly further than their strong reader siblings. Transcriptome analyses of NPCs and excitatory neurons 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 migration in RD and point to specific genes contributing to the altered cell phenotypes.