Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function

  1. Dimitar Kostadinov
  2. Joshua R Sanes  Is a corresponding author
  1. Harvard University, United States


Dendritic and axonal arbors of many neuronal types exhibit self-avoidance, in which branches repel each other. In some cases, these neurites interact with those of neighboring neurons, a phenomenon called self/non-self discrimination. The functional roles of these processes remain unknown. Here, we used retinal starburst amacrine cells (SACs), critical components of a direction-selective circuit, to address this issue. In SACs, both processes are mediated by the gamma-protocadherins (Pcdhgs), a family of 22 recognition molecules. We manipulated Pcdhg expression in SACs and recorded from them and their targets, direction-selective ganglion cells (DSGCs). SACs form autapses when self-avoidance is disrupted and fail to form connections with other SACs when self/non-self discrimination is perturbed. Pcdhgs are also required to prune connections between closely spaced SACs. These alterations degrade the direction selectivity of DSGCs. Thus, self-avoidance, self/non-self discrimination, and synapse elimination are essential for proper function of a circuit that computes directional motion.

Article and author information

Author details

  1. Dimitar Kostadinov

    Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Joshua R Sanes

    Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Kang Shen, Howard Hughes Medical Institute, Stanford University, United States


Animal experimentation: Animals were used in accordance with NIH guidelines and protocols approved by Institutional Animal Use and Care Committee at Harvard University (IACUC protocol #24-10).Animals were euthanized by intraperitoneal injection of pentobarbital or euthasol.

Version history

  1. Received: May 24, 2015
  2. Accepted: July 2, 2015
  3. Accepted Manuscript published: July 3, 2015 (version 1)
  4. Version of Record published: August 25, 2015 (version 2)


© 2015, Kostadinov & Sanes

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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  1. Dimitar Kostadinov
  2. Joshua R Sanes
Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function
eLife 4:e08964.

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