title: Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors.
abstract: In vivo axon pathfinding mechanisms in the neuron-dense brain remain relatively poorly characterized. We study the Drosophila mushroom body (MB) axons, whose α and β branches connect to different brain areas. We show that the Ryk family WNT5 receptor, DRL (derailed), which is expressed in the dorsomedial lineages, brain structure precursors adjacent to the MBs, is required for MB α branch axon guidance. DRL acts to capture and present WNT5 to MB axons rather than transduce a WNT5 signal. DRL's ectodomain must be cleaved and shed to guide α axons. DRL-2, another Ryk, is expressed within MB axons and functions as a repulsive WNT5 signaling receptor. Finally, our biochemical data support the existence of a ternary complex composed of the cleaved DRL ectodomain, WNT5, and DRL-2. Thus, the interaction of MB-extrinsic and -intrinsic Ryks via their common ligand acts to guide MB α axons.
authors.affiliation: Institute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Reynaud
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Liza L
authors.initials: LL
authors.lastname: Lahaye
authors.affiliation: Institute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Boulanger
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Iveta M
authors.initials: IM
authors.lastname: Petrova
authors.affiliation: Institute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Marquilly
authors.affiliation: Institute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Flandre
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Tania
authors.initials: T
authors.lastname: Martianez
authors.affiliation: Institute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Privat
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Jasprina N
authors.initials: JN
authors.lastname: Noordermeer
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. Electronic address: l.g.fradkin@lumc.nl.
authors.forename: Lee G
authors.initials: LG
authors.lastname: Fradkin
authors.affiliation: Institute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, France. Electronic address: jean-maurice.dura@igh.cnrs.fr.
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Dura
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D024521:Mushroom Bodies / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C491438:Wnt5 protein, Drosophila; C094492:DRL protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases