Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuron. 2014 Mar 5;81(5):1040-1056. doi: 10.1016/j.neuron.2014.01.009.

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

Author information

1
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.
2
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
3
Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
4
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMR_S968, CNRS_UMR7210, Institut de la Vision, 750012, Paris, France.
5
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.

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.

PMID:
24607227
PMCID:
PMC3963503
DOI:
10.1016/j.neuron.2014.01.009
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center