Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors

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 dorsom...

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Main Authors: Elodie Reynaud, Liza L. Lahaye, Ana Boulanger, Iveta M. Petrova, Claire Marquilly, Adrien Flandre, Tania Martianez, Martin Privat, Jasprina N. Noordermeer, Lee G. Fradkin, Jean-Maurice Dura
Format: Article
Language:English
Published: Elsevier 2015-05-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124715004362
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author Elodie Reynaud
Liza L. Lahaye
Ana Boulanger
Iveta M. Petrova
Claire Marquilly
Adrien Flandre
Tania Martianez
Martin Privat
Jasprina N. Noordermeer
Lee G. Fradkin
Jean-Maurice Dura
author_facet Elodie Reynaud
Liza L. Lahaye
Ana Boulanger
Iveta M. Petrova
Claire Marquilly
Adrien Flandre
Tania Martianez
Martin Privat
Jasprina N. Noordermeer
Lee G. Fradkin
Jean-Maurice Dura
author_sort Elodie Reynaud
collection DOAJ
description 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.
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spelling doaj.art-200f617be84d40088ed02af0586f12522022-12-21T23:41:38ZengElsevierCell Reports2211-12472015-05-011181293130410.1016/j.celrep.2015.04.035Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage PrecursorsElodie Reynaud0Liza L. Lahaye1Ana Boulanger2Iveta M. Petrova3Claire Marquilly4Adrien Flandre5Tania Martianez6Martin Privat7Jasprina N. Noordermeer8Lee G. Fradkin9Jean-Maurice Dura10Institute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, FranceDepartment of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsInstitute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, FranceDepartment of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsInstitute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, FranceInstitute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, FranceDepartment of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsInstitute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, FranceDepartment of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsDepartment of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsInstitute of Human Genetics, UPR1142, CNRS, 141, rue de la Cardonille, 34396 Montpellier, FranceIn 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.http://www.sciencedirect.com/science/article/pii/S2211124715004362
spellingShingle Elodie Reynaud
Liza L. Lahaye
Ana Boulanger
Iveta M. Petrova
Claire Marquilly
Adrien Flandre
Tania Martianez
Martin Privat
Jasprina N. Noordermeer
Lee G. Fradkin
Jean-Maurice Dura
Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors
Cell Reports
title Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors
title_full Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors
title_fullStr Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors
title_full_unstemmed Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors
title_short Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors
title_sort guidance of drosophila mushroom body axons depends upon drl wnt receptor cleavage in the brain dorsomedial lineage precursors
url http://www.sciencedirect.com/science/article/pii/S2211124715004362
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