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Ephrin-b1 controls the columnar distribution of cortical pyramidal neurons by restricting their tangential migration.

par Dimidschstein, Jordane ;Passante, Lara ;Dufour, Audrey ;Van Den Ameele, Jelle ;Tiberi, Luca ;Hrechdakian, Tatyana;Adams, Ralf;Klein, Rüdiger;Lie, Dieter Chichung;Jossin, Yves;Vanderhaeghen, Pierre
Référence Neuron, 79, 6, page (1123-1135)
Publication Publié, 2013-09

Article révisé par les pairs

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Résumé :

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.