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

Publication Type:

Journal Article

Source:

Neuron, Volume 79, Issue 6, p.1123-35 (2013)

Keywords:

2013, Age Factors, Animals, Animals, Newborn, Basic Sciences Division, Carrier Proteins, Cell Adhesion, Cell Cycle Proteins, Cell Movement, Center-Authored Paper, Cerebral Cortex, Electroporation, Embryo, Mammalian, Ephrin-B1, Female, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Homeodomain Proteins, Immunoprecipitation, Male, March 2014, MICE, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Nuclear Proteins, PREGNANCY, Pyramidal Cells, Repressor Proteins

Abstract:

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.