N-cadherin sustains motility and polarity of future cortical interneurons during tangential migration.
In the developing brain, cortical GABAergic interneurons migrate long distances from the medial ganglionic eminence (MGE) in which they are generated, to the cortex in which they settle. MGE cells express the cell adhesion molecule N-cadherin, a homophilic cell-cell adhesion molecule that regulates numerous steps of brain development, from neuroepithelium morphogenesis to synapse formation. N-cadherin is also expressed in embryonic territories crossed by MGE cells during their migration. In this study, we demonstrate that N-cadherin is a key player in the long-distance migration of future cortical interneurons. Using N-cadherin-coated substrate, we show that N-cadherin-dependent adhesion promotes the migration of mouse MGE cells in vitro. Conversely, mouse MGE cells electroporated with a construct interfering with cadherin function show reduced cell motility, leading process instability, and impaired polarization associated with abnormal myosin IIB dynamics. In vivo, the capability of electroporated MGE cells to invade the developing cortical plate is altered. Using genetic ablation of N-cadherin in mouse embryos, we show that N-cadherin-depleted MGEs are severely disorganized. MGE cells hardly exit the disorganized proliferative area. N-cadherin ablation at the postmitotic stage, which does not affect MGE morphogenesis, alters MGE cell motility and directionality. The tangential migration to the cortex of N-cadherin ablated MGE cells is delayed, and their radial migration within the cortical plate is perturbed. Altogether, these results identify N-cadherin as a pivotal adhesion substrate that activates cell motility in future cortical interneurons and maintains cell polarity over their long-distance migration to the developing cortex.
Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 839, Institut du Fer à Moulin, 75005 Paris, France, Université Pierre et Marie Curie-Paris 6, 75005 Paris, France, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan, Wolfson Institute for Biomedical Research and Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom, and Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Camilla
C
Luccardini
Laetitia
L
Hennekinne
Lucie
L
Viou
Mitsutoshi
M
Yanagida
Fujio
F
Murakami
Nicoletta
N
Kessaris
Xufei
X
Ma
Robert S
RS
Adelstein
René-Marc
RM
Mège
Christine
C
Métin
D000818:Animals; D015820:Cadherins / Q000172:deficiency / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D005544:Forecasting; D006801:Humans; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D011247:Pregnancy
D015820:Cadherins