title: Slit and Receptor Tyrosine Phosphatase 69D Confer Spatial Specificity to Axon Branching via Dscam1.
abstract: Axonal branching contributes substantially to neuronal circuit complexity. Studies in Drosophila have shown that loss of Dscam1 receptor diversity can fully block axon branching in mechanosensory neurons. Here we report that cell-autonomous loss of the receptor tyrosine phosphatase 69D (RPTP69D) and loss of midline-localized Slit inhibit formation of specific axon collaterals through modulation of Dscam1 activity. Genetic and biochemical data support a model in which direct binding of Slit to Dscam1 enhances the interaction of Dscam1 with RPTP69D, stimulating Dscam1 dephosphorylation. Single-growth-cone imaging reveals that Slit/RPTP69D are not required for general branch initiation but instead promote the extension of specific axon collaterals. Hence, although regulation of intrinsic Dscam1-Dscam1 isoform interactions is essential for formation of all mechanosensory-axon branches, the local ligand-induced alterations of Dscam1 phosphorylation in distinct growth-cone compartments enable the spatial specificity of axon collateral formation.
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium; Department of Oncology, School of Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors: Dan
authors: D
authors: Dascenco
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium; Department of Oncology, School of Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium; Institute of Biochemistry, Christian-Albrechts-University of Kiel, Olshausenstr. 40, 24098 Kiel, Germany.
authors: Maria-Luise
authors: ML
authors: Erfurth
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium; Department of Oncology, School of Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors: Azadeh
authors: A
authors: Izadifar
authors: Biology/MS 314, University of Nevada, Reno, NV 89557, USA.
authors: Minmin
authors: M
authors: Song
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium; Department of Oncology, School of Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium; Department of Biology, Chemistry & Pharmacy, Free University Berlin, Takustr. 3, 14195 Berlin, Germany.
authors: Sonja
authors: S
authors: Sachse
authors: Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors: Rachel
authors: R
authors: Bortnick
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium; Department of Oncology, School of Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors: Olivier
authors: O
authors: Urwyler
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium; Department of Oncology, School of Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors: Milan
authors: M
authors: Petrovic
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors: Derya
authors: D
authors: Ayaz
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors: Haihuai
authors: H
authors: He
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium; Department of Oncology, School of Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors: Yoshiaki
authors: Y
authors: Kise
authors: Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors: Franziska
authors: F
authors: Thomas
authors: Biology/MS 314, University of Nevada, Reno, NV 89557, USA.
authors: Thomas
authors: T
authors: Kidd
authors: Neuronal Wiring Laboratory, VIB, Herestraat 49, 3000 Leuven, Belgium; Department of Oncology, School of Medicine, University of Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: dietmar.schmucker@vib-kuleuven.be.
authors: Dietmar
authors: D
authors: Schmucker
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D054557:Receptor-Like Protein Tyrosine Phosphatases / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C066819:sli protein, Drosophila; C482451:PTP69D protein, Drosophila; D054557:Receptor-Like Protein Tyrosine Phosphatases