title: Frazzled promotes growth cone attachment at the source of a Netrin gradient in theDrosophilavisual system.
abstract: Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In theDrosophilavisual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it. Thus, despite the graded ligand distribution along the guidance path, Net-Fra is not used for chemoattraction. Based on findings in other systems, we propose that adhesion to substrate-bound Net underlies both long- and short-range Net-Fra-dependent guidancein vivo, thereby eroding the distinction between them.
authors.affiliation: Department of Biological Chemistry, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Orkun
authors.initials: O
authors.lastname: Akin
authors.affiliation: Department of Biological Chemistry, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: S Lawrence
authors.identifier: http://orcid.org/0000-0001-5630-7181
authors.initials: SL
authors.lastname: Zipursky
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000235:genetics; D001369:Axons / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000378:metabolism*; D000075386:Netrin Receptors / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002630:Chemotactic Factors; D029721:Drosophila Proteins; D000075386:Netrin Receptors; D012097:Repressor Proteins; C000617310:fra protein, Drosophila; C417033:net protein, Drosophila
keywords: D. melanogaster; axon guidance; developmental biology; live imaging; neuroscience; stem cells; two-photon microscopy