Wnt signaling regulates multipolar-to-bipolar transition of migrating neurons in the cerebral cortex.
The precise timing of pyramidal cell migration from the ventricular germinal zone to the cortical plate is essential for establishing cortical layers, and migration errors can lead to neurodevelopmental disorders underlying psychiatric and neurological diseases. Here, we report that Wnt canonical as well as non-canonical signaling is active in pyramidal precursors during radial migration. We demonstrate using constitutive and conditional genetic strategies that transient downregulation of canonical Wnt/β-catenin signaling during the multipolar stage plays a critical role in polarizing and orienting cells for radial migration. In addition, we show that reduced canonical Wnt signaling is triggered cell autonomously by time-dependent expression of Wnt5A and activation of non-canonical signaling. We identify ephrin-B1 as a canonical Wnt-signaling-regulated target in control of the multipolar-to-bipolar switch. These findings highlight the critical role of Wnt signaling activity in neuronal positioning during cortical development.
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland.
Michael
M
Boitard
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland.
Riccardo
R
Bocchi
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland.
Kristof
K
Egervari
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland.
Volodymyr
V
Petrenko
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland.
Beatrice
B
Viale
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland.
Stéphane
S
Gremaud
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland.
Eloisa
E
Zgraggen
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland.
Patrick
P
Salmon
Department of Neurosciences, University of Geneva Medical School, 1211 Geneva, Switzerland. Electronic address: jozsef.kiss@unige.ch.
Jozsef Z
JZ
Kiss
D000818:Animals; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D036387:Ephrin-B1 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020825:T-Box Domain Proteins / Q000378:metabolism; D059008:Time-Lapse Imaging; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000378:metabolism
D036387:Ephrin-B1; D034741:RNA, Small Interfering; D020825:T-Box Domain Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; D051176:beta Catenin