TY - JOUR T1 - NEUROD2 represses Reelin expression and controls dendrite orientation during cortical radial migration JF - bioRxiv DO - 10.1101/651273 SP - 651273 AU - Gizem Guzelsoy AU - Cansu Akkaya AU - Dila Atak AU - Cory D. Dunn AU - Alkan Kabakcioglu AU - Nurhan Ozlu AU - Gulayse Ince-Dunn Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/27/651273.abstract N2 - Excitatory neurons of the mammalian cerebral cortex are organized into six functional layers characterized by unique patterns of connectivity, as well as distinctive physiological and morphological properties. Developmentally, cortical layers emerge after a highly regulated neuronal migration process from the ventricular zone, where proliferating cells reside, toward the superficial layers, where the early cortex starts to develop. Importantly, defects in this radial migration process have been implicated in neurodevelopmental and psychiatric diseases. Here we report that during the final stages of migration, transcription factor Neurogenic Differentiation 2 (Neurod2) contributes to terminal cellular positioning within the cortical plate and alignment of nascent dendrites toward the marginal zone. In mice, in utero knockdown of Neurod2 results in misaligned primary dendrites of migrating neurons within the nascent cortical plate. Our ChIP-Seq and RNA-Seq analyses of NEUROD2-regulated genes in the developing cortex identify Reelin (Reln), a critical regulator of neuronal migration, as a key downstream target. NEUROD2 binds to conserved E-box elements in multiple introns of the Reln gene, and binding is associated with suppression of gene expression. These data reveal a new role for NEUROD2 during neuronal migration and suggest that fine-tuning of Reln gene expression in migrating neurons is important for terminal cellular positioning of neurons upon arrival to the cortical plate. ER -