Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling.
Axons travel to their targets in bundles or fascicles, but the molecules regulating fasciculation remain incompletely characterized. We found that Slit2 and its Robo receptors are expressed by motor axons, and that inactivation of Slit2 or Robo1 and Robo2 in mice caused axons to defasciculate prematurely at muscle targets. In vitro, Slit2 secreted by motoneurons regulated fasciculation through Robo1 and Robo2. These results support the idea that Slit2 promotes axon fasciculation via an autocrine and/or juxtaparacrine mechanism.
Division of Research, Genentech, South San Francisco, California, USA.
Alexander
A
Jaworski
Marc
M
Tessier-Lavigne
D000818:Animals; D019898:Autocrine Communication / Q000235:genetics; D001369:Axons / Q000502:physiology*; D003964:Diaphragm / Q000166:cytology*; D004622:Embryo, Mammalian; D005207:Fasciculation / Q000235:genetics / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology*; D018482:Muscle, Skeletal / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000172:deficiency; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic / Q000172:deficiency; D015398:Signal Transduction / Q000235:genetics*; D014404:Tubulin / Q000378:metabolism; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D014404:Tubulin; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C120010:Slit1 protein, mouse; C432251:Slit3 protein, mouse; C462941:beta3 tubulin, mouse