Heparan sulfate proteoglycan syndecan promotes axonal and myotube guidance by slit/robo signaling.
Slit, the ligand for the Roundabout (Robo) receptors, is secreted from midline cells of the Drosophila central nervous system (CNS). 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. 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. Biochemical studies suggest that guidance activity requires cell-surface heparan sulfate to promote binding of mammalian Slit/Robo homologs. Here, we report that the Drosophila homolog of Syndecan (reviewed in ), 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.
Steigemann
Patrick
P
Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, 37077 Goettingen, Germany.
Molitor
Andreas
A
Fellert
Sonja
S
Jäckle
Herbert
H
Vorbrüggen
Gerd
G
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D053667:Syndecans; D000097905:Roundabout Proteins
D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D011971:Receptors, Immunologic; D053667:Syndecans; D000097905:Roundabout Proteins; C066819:sli protein, Drosophila