A conserved role for Syntaxin-1 in pre- and post-commissural midline axonal guidance in fly, chick, and mouse

by Oriol Ros, Pablo Jos é Barrecheguren, Tiziana Cotrufo, Martina Schaettin, Cristina Roselló-Busquets, Alba Vílchez-Acosta, Marc Hernaiz-Llorens, Ramón Martínez-Marmol, Fausto Ulloa, Esther T. Stoeckli, Sofia J. Araújo, Eduardo Soriano Axonal growth and guidance rely on correct growth cone responses to guidance cues. Unlike the signaling cascades that link axonal growth to cytoskeletal dynamics, little is known about the crosstalk mechanisms between guidance and membrane dynamics and turnover. Recent studies indicate that wherea s axonal attraction requires exocytosis, chemorepulsion relies on endocytosis. Indeed, our own studies have shown that Netrin-1/Deleted in Colorectal Cancer (DCC) signaling triggers exocytosis through the SNARE Syntaxin-1 (STX1). However, limitedin vivo evidence is available about the role of SNARE proteins in axonal guidance. To address this issue, here we systematically deleted SNARE genes in three species. We show that loss-of-function of STX1 results in pre- and post-commissural axonal guidance defects in the midline of fly, chick, and mouse embryos. Inactivation of VAMP2, Ti-VAMP, and SNAP25 led to additional abnormalities in axonal guidance. We also confirmed that STX1 loss-of-function results in reduced sensitivity of commissural axons to Slit-2 and Netrin-1. Finally, genetic interaction studies inDrosophila show that STX1 interacts with both the Netrin-1/DCC and Robo/Slit pathways. Our data provide evidence of an evolutionarily conserv...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research