Dendrite self-avoidance requires cell-autonomous slit/robo signaling in cerebellar purkinje cells

Neuron. 2014 Mar 5;81(5):1040-1056. doi: 10.1016/j.neuron.2014.01.009.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebellum / cytology
  • Coculture Techniques
  • Dendrites / metabolism*
  • Gene Expression Regulation, Developmental
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neural Pathways / cytology
  • Neural Pathways / physiology
  • Organ Culture Techniques
  • Phenotype
  • Purkinje Cells / metabolism*
  • Purkinje Cells / ultrastructure*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / physiology*


  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Robo2 protein, mouse
  • Slit homolog 2 protein