Heparan Sulfate Proteoglycan Syndecan Promotes Axonal and Myotube Guidance by Slit/Robo Signaling

• Published in: Current biology 2004-02, Vol.14 (3), p.225-230
• Main Authors: Steigemann, Patrick, Molitor, Andreas, Fellert, Sonja, Jäckle, Herbert, Vorbrüggen, Gerd
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Axons - physiology; Cell Movement - physiology; Drosophila; Drosophila Proteins; In Situ Hybridization; Membrane Glycoproteins - metabolism; Muscle Fibers, Skeletal - physiology; Nerve Tissue Proteins - metabolism; Proteoglycans - metabolism; Receptors, Immunologic - metabolism; Roundabout Proteins; Signal Transduction - physiology; Syndecans
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2004.01.006

Slit, the ligand for the Roundabout (Robo) receptors [1–3], is secreted from midline cells of the Drosophila central nervous system (CNS) [4]. It acts as a short-range repellent that controls midline crossing of axons and allows growth cones to select specific pathways along each side of the midline [1, 3]. In addition, Slit directs the migration of muscle precursors and ventral branches of the tracheal system, showing that it provides long-range activity beyond the limit of the developing CNS [2, 5, 6]. Biochemical studies suggest that guidance activity requires cell-surface heparan sulfate to promote binding of mammalian Slit/Robo homologs [7, 8]. Here, we report that the Drosophila homolog of Syndecan (reviewed in [9]), a heparan sulfate proteoglycan (HSPG), is required for proper Slit signaling. We generated syndecan (sdc) mutations and show that they affect all aspects of Slit activity and cause robo-like phenotypes. sdc interacts genetically with robo and slit, and double mutations cause a synergistic strengthening of the single-mutant phenotypes. The results suggest that Syndecan is a necessary component of Slit/Robo signaling and is required in the Slit target cells.