Vangl2 acts at the interface between actin and N-cadherin to modulate mammalian neuronal outgrowth. Steve Dos-Santos Carvalho, Maite M Moreau, Yeri Esther Hien, Michael Garcia, Nathalie Aubailly, Deborah J Henderson, Vincent Studer, Nathalie Sans, Olivier Thoumine, Mireille Montcouquiol. eLife. 2020-01-07. 9.
Here, we show that an early deletion of vangl2 in neuronal progenitors of the forebrain leads to the spatially restricted deficit of only two commissural axon bundles. Mechanistically, we show that the absence of vangl2 leads to an increase in axonal outgrowth due to a reduced turnover of N-cadherin, and a better coupling between the adhesion molecule and the dynamic actin flow in the growth cone. Our results support a model in which Vangl2 acts as a regulator of membrane protein endocytosis and junctional remodeling during growth cone exploration, thereby modulating its outgrowth.
This study benefited from a close collaboration between the groups of Montcouquiol/Sans (Neurocentre Magendie), O. Thoumine (IINS), and V. Studer (IINS), funded by the Labex BRAIN (project PCP Compass).