The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain development has remained controversial. Humans with mutations show profound alterations in cortical lamination, whereas in mouse, RNAi-mediated knockdown but not germline knockout shows abnormal positioning of cortical neurons. Here, we report that the doublecortin-like kinase (Dclk) gene functions in a partially redundant pathway with Dcx in the formation of axonal projections across the midline and migration of cortical neurons. Dosage-dependent genetic effects were observed in both interhemispheric connectivity and migration of cortically and subcortically derived neurons. Surprisingly, RNAi-mediated knockdown of either gene results in similar migration defects. These results indicate the Dcx microtubule-associated protein family is required for proper neuronal migration and axonal wiring.
