title: Dendrite self-avoidance requires cell-autonomous slit/robo signaling in cerebellar purkinje cells.
abstract: Dendrites from the same neuron usually develop nonoverlapping patterns by self-avoidance, a process requiring contact-dependent recognition and repulsion. Recent studies have implicated homophilic interactions of cell surface molecules, including Dscams and Pcdhgs, in self-recognition, but repulsive molecular mechanisms remain obscure. Here, we report a role for the secreted molecule Slit2 and its receptor Robo2 in self-avoidance of cerebellar Purkinje cells (PCs). Both molecules are highly expressed by PCs, and their deletion leads to excessive dendrite self-crossing without affecting arbor size and shape. This cell-autonomous function is supported by the boundary-establishing activity of Slit in culture and the phenotype rescue by membrane-associated Slit2 activities. Furthermore, genetic studies show that they act independently from Pcdhg-mediated recognition. Finally, PC-specific deletion of Robo2 is associated with motor behavior alterations. Thus, our study uncovers a local repulsive mechanism required for self-avoidance and demonstrates the molecular complexity at the cell surface in dendritic patterning.
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Neuroscience Graduate Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gibson
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tymanskyj
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Neuroscience Graduate Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Yuan
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Haiwen C
authors.initials: HC
authors.lastname: Leung
authors.affiliation: Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Lefebvre
authors.affiliation: Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S968, CNRS_UMR7210, Institut de la Vision, 750012, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Chédotal
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Neuroscience Graduate Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: le.ma@usc.edu.
authors.forename: Le
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology; D018920:Coculture Techniques; D003712:Dendrites / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009924:Organ Culture Techniques; D010641:Phenotype; D011689:Purkinje Cells / Q000378:metabolism* / Q000648:ultrastructure*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000098552:Slit Homolog 2 Protein; D000097905:Roundabout Proteins
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000098552:Slit Homolog 2 Protein; C498888:Robo2 protein, mouse; D000097905:Roundabout Proteins