title: Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex.
abstract: The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body.
authors: Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Physiology and Biophysics Department, Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Independencia 1027, 8380453 Santiago, Chile.
authors: Carlos
authors: C
authors: Oliva
authors: Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium.
authors: Alessia
authors: A
authors: Soldano
authors: Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium.
authors: Natalia
authors: N
authors: Mora
authors: Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium.
authors: Natalie
authors: N
authors: De Geest
authors: Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium.
authors: Annelies
authors: A
authors: Claeys
authors: Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Neuronal Wiring Laboratory, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Institute of Biochemistry, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
authors: Maria-Luise
authors: ML
authors: Erfurth
authors: Physiology and Biophysics Department, Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Independencia 1027, 8380453 Santiago, Chile.
authors: Jimena
authors: J
authors: Sierralta
authors: Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium.
authors: Ariane
authors: A
authors: Ramaekers
authors: Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Neuronal Wiring Laboratory, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium.
authors: Dan
authors: D
authors: Dascenco
authors: Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et la moelle (ICM) - Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, 75013 Paris, France.
authors: Radoslaw K
authors: RK
authors: Ejsmont
authors: Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Neuronal Wiring Laboratory, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium.
authors: Dietmar
authors: D
authors: Schmucker
authors: Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
authors: Natalia
authors: N
authors: Sanchez-Soriano
authors: Laboratory of Neurogenetics, VIB Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie (VIB), 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et la moelle (ICM) - Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, 75013 Paris, France. Electronic address: bassem.hassan@icm-institute.org.
authors: Bassem A
authors: BA
authors: Hassan
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D007814:Larva / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D024521:Mushroom Bodies / Q000378:metabolism; D009415:Nerve Net / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019581:Neuropil / Q000378:metabolism*; D010641:Phenotype; D054557:Receptor-Like Protein Tyrosine Phosphatases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D000097905:Roundabout Proteins
chemical_list: D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D054557:Receptor-Like Protein Tyrosine Phosphatases; D011971:Receptors, Immunologic; C421244:robo3 protein, Drosophila; D000097905:Roundabout Proteins; C066819:sli protein, Drosophila; C482451:PTP69D protein, Drosophila
keywords: Drosophila; axon growth; axon guidance; brain wiring; mushroom body; neural circuit development; receptor protein tyrosine phosphatase; robo; slit