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Ephrin-B1 controls the spatial distribution of cortical pyramidal neurons by restricting their tangential migration

par Dimidschstein, Jordane
Président du jury Vassart, Gilbert
Promoteur Vanderhaeghen, Pierre
Publication Non publié, 2012-08-29

Thèse de doctorat

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Résumé :

During development of the cerebral cortex, the various neuronal subtypes have to reach their correct final position in the post mitotic compartment where they complete their maturation and eventually establish functional networks. Precise positioning of individual neurons is acquired through tight regulation of the multiple transitions that neurons undergo on their way to the cortical plate. Neurons of the cerebral cortex are organized in layers and columns. Although several molecular mechanisms have been identified that control the final position of neurons along the radial dimension of the cortex (i.e. layer specificity), much less is known about how their final tangential, or mediolateral, distribution is controlled. However this may have a direct impact on the structural and functional organization of cortical columns, since sister neurons derived from the same progenitor display selective patterns of connectivity with each other and/or share similar functional properties. Here we studied the role of B-ephrins in the control of migration of cortical pyramidal neurons. Gain of function experiments using in utero electroporation of ephrin-B1 revealed a striking alteration of the tangential distribution of pyramidal neurons during the multipolar stage of radial migration, resulting in clustering of the pyramidal neurons in the cortical plate. Conversely, clonal analysis of migrating neurons in ephrin-B1 knockout mice showed a wider mediolateral dispersion of cortical neurons. Static and dynamic analyses of migrating neurons revealed that ephrin-B1 modulates the morphology of pyramidal neurons during their multipolar phase, thereby restricting their tangential migration at that stage. Our results demonstrate that ephrin-B1 is a specific inhibitor of non-radial migration of pyramidal neurons, thereby controlling the pattern of cortical columns. These data shed new light on this important aspect of pyramidal neuronal migration, and illustrate how alterations of patterns of migration can affect cortical column organization.