redundant mechanisms for regulation of midline crossing in drosophila冗余机制的监管中线穿越在果蝇.pdfVIP

Redundant Mechanisms for Regulation of Midline Crossing in Drosophila ¤ Giorgio F. Gilestro * Research Institute of Molecular Pathology (IMP), Vienna, Austria Abstract During development, all neurons have to decide on whether to cross the longitudinal midline to project on the contralateral side of the body. In vertebrates and invertebrates regulation of crossing is achieved by interfering with Robo signalling either through sorting and degradation of the receptor, in flies, or through silencing of its repulsive activity, in vertebrates. Here I show that in Drosophila a second mechanism of regulation exists that is independent from sorting. Using in vitro and in vivo assays I mapped the region of Robo that is sufficient and required for its interaction with Comm, its sorting receptor. By modifying that region, I generated new forms of Robo that are insensitive to Comm sorting in vitro and in vivo, yet still able to normally translate repulsive activity in vivo. Using gene targeting by homologous recombination I created new conditional alleles of robo that are sorting defective (roboSD). Surprisingly, expression of these modified proteins results in phenotypically normal flies, unveiling a sorting independent mechanism of regulation. Citation: Gilestro GF (2008) Redundant Mechanisms for Regulation of Midline Crossing in Drosophila. PLoS ONE 3(11): e3798. doi:10.1371/journal.pone.0003798 Editor: Francois Schweisguth, Institut Pasteur, France Received August 19, 2008; Accepted November 5, 2008; Published November 24, 2008 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. F