title: Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila.
abstract: The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance.
authors.affiliation: MRC Centre for Developmental Neurobiology, New Hunts House, King's College, London, SE1 1UL, UK.
authors.forename: Marie-Sophie
authors.initials: MS
authors.lastname: Cate
authors.affiliation: MRC Centre for Developmental Neurobiology, New Hunts House, King's College, London, SE1 1UL, UK.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Gajendra
authors.affiliation: MRC Centre for Developmental Neurobiology, New Hunts House, King's College, London, SE1 1UL, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Alsbury
authors.affiliation: MSZ Universitat Würzburg, Versbacher Strasse 5, Würzberg 97078, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Raabe
authors.affiliation: MRC Centre for Developmental Neurobiology, New Hunts House, King's College, London, SE1 1UL, UK guy.tear@kcl.ac.uk.
authors.forename: Guy
authors.initials: G
authors.lastname: Tear
authors.affiliation: Howard Hughes Medical Institute, Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA Smurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002490:Central Nervous System / Q000196:embryology; D029721:Drosophila Proteins / Q000172:deficiency / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008938:Mitosis; D024521:Mushroom Bodies / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009414:Nerve Growth Factors / Q000172:deficiency / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000075388:Netrin-1; D000075385:Netrins; D010641:Phenotype; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D008565:Membrane Proteins; C411670:Mud protein, Drosophila; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C000617352:NetA protein, Drosophila; C583437:NetB protein, Drosophila; D000075385:Netrins; C405164:Pins protein, Drosophila; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1
keywords: Axon guidance; Drosophila; LIN-5; Midline; Mud; Netrin; NuMA