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.
Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 808 Route de Lennik, B-1070 Brussels, Belgium.
Jordane
J
Dimidschstein
Lara
L
Passante
Audrey
A
Dufour
Jelle
J
van den Ameele
Luca
L
Tiberi
Tatyana
T
Hrechdakian
Ralf
R
Adams
Rüdiger
R
Klein
Dieter Chichung
DC
Lie
Yves
Y
Jossin
Pierre
P
Vanderhaeghen
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D002540:Cerebral Cortex / Q000166:cytology*; D018274:Electroporation; D004622:Embryo, Mammalian; D036387:Ephrin-B1 / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D011247:Pregnancy; D017966:Pyramidal Cells / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D036387:Ephrin-B1; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C501070:RBBP8 protein, mouse; C000624101:Cux1 protein, mouse