Ephrin-B1 Controls the Columnar Distribution of Cortical Pyramidal Neurons by Restricting Their Tangential Migration

Neurons of the cerebral cortex are organized in layers and columns. Unlike laminar patterning, the mechanisms underlying columnar organization remain largely unexplored. Here, we show that ephrin-B1 plays a key role in this process through the control of nonradial steps of migration of pyramidal neurons. In vivo gain of function of ephrin-B1 resulted in a reduction of tangential motility of pyramidal neurons, leading to abnormal neuronal clustering. Conversely, following genetic disruption of ephrin-B1, cortical neurons displayed a wider lateral dispersion, resulting in enlarged ontogenic columns. Dynamic analyses revealed that ephrin-B1 controls the lateral spread of pyramidal neurons by limiting neurite extension and tangential migration during the multipolar phase. Furthermore, we identified P-Rex1, a guanine-exchange factor for Rac3, as a downstream ephrin-B1 effector required to control migration during the multipolar phase. Our results demonstrate that ephrin-B1 inhibits nonradial migration of pyramidal neurons, thereby controlling the pattern of cortical columns. •Ephrin-B1 reverse signaling restricts tangential migration of pyramidal neurons•Ephrin-B1 restricts neurite extension during multipolar phase of migration•Ephrin-B1 mutant mice display abnormally wide ontogenic cortical columns•P-Rex1 is a key effector of ephrin-B1 to control migration of pyramidal neurons Cortical neurons are organized in layers and columns. Unlike laminar patterning, the mechanisms underlying columnar organization remain largely unknown. Dimidschstein et al. describe how signaling proteins ephrin-B1 and P-Rex-1 control this process by regulating a specific key step of nonradial migration.