The specific causes of dyslexia are not yet known. Recent genetic and neurobiological studies strengthen a working hypothesis that dyslexia is caused by early developmental disruptions that subsequently cause functional impairments in neocortical circuits. Within the past four years, 4 candidate dyslexia susceptibility genes with roles in neuronal development have been proposed (DYX1C1, KIAA0319, DCDC2 and ROBO1). Rodent homologs of three of these, Dyxld, Kiaa0319 and Dcdc2 have been shown by our group to play a role in neuronal migration in'developing neocortex, and Robol was previously shown to be important for axon growth and guidance. The three aims of this project will further define the cellular and developmental roles of Dyxld. The proposed experiments will define the components of neuronal migration and differentiation regulated by Dyxld, and identify functional links between Dyxld and other proteins essential to migration.
The aims will be executed by a combination of in utero RNAi, imaging, protein-protein interaction assays, and cell culture approaches. Novel in vivo conditional RNAi and overexpression methods will be used to explore the temporal dependence of Dyxld function, and potential developmental reversibility of Dyx1c1 dysfunction. Together, these experiments will lead to a comprehensive molecular and cellular understanding of the function of a gene linked to reading and learning disability.
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