N-Cadherin Sustains Motility and Polarity of Future Cortical Interneurons during Tangential Migration

Autor: Laetitia Hennekinne, René-Marc Mège, Robert S. Adelstein, Fujio Murakami, Mitsutoshi Yanagida, Lucie Viou, Christine Métin, Xufei Ma, Nicoletta Kessaris, Camilla Luccardini
Rok vydání: 2013
Předmět:
Zdroj: The Journal of Neuroscience. 33:18149-18160
ISSN: 1529-2401
0270-6474
Popis: 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 cellsin 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 ofN-cadherinin mouse embryos, we show thatN-cadherin-depleted MGEs are severely disorganized. MGE cells hardly exit the disorganized proliferative area.N-cadherinablation at the postmitotic stage, which does not affect MGE morphogenesis, alters MGE cell motility and directionality. The tangential migration to the cortex ofN-cadherinablated 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.
Databáze: OpenAIRE