Regulation of subcellular dendritic synapse specificity by axon guidance cues

  1. Emily C Sales
  2. Emily L Heckman
  3. Timothy L Warren
  4. Chris Q Doe  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Oregon, United States

Abstract

Neural circuit assembly occurs with subcellular precision, yet the mechanisms underlying this precision remain largely unknown. Subcellular synaptic specificity could be achieved by molecularly distinct subcellular domains that locally regulate synapse formation, or by axon guidance cues restricting access to one of several acceptable targets. We address these models using two Drosophila neurons: the dbd sensory neuron and the A08a interneuron. In wild-type larvae, dbd synapses with the A08a medial dendrite but not the A08a lateral dendrite. dbd-specific overexpression of the guidance receptors Unc-5 or Robo-2 results in lateralization of the dbd axon, which forms anatomical and functional monosynaptic connections with the A08a lateral dendrite. We conclude that axon guidance cues, not molecularly distinct dendritic arbors, are a major determinant of dbd-A08a subcellular synapse specificity.

Data availability

Code is deposited to the GitHub repository named in the text

The following data sets were generated

Article and author information

Author details

  1. Emily C Sales

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Emily L Heckman

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Timothy L Warren

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4429-4106
  4. Chris Q Doe

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    For correspondence
    cdoe@uoregon.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5980-8029

Funding

Howard Hughes Medical Institute

  • Chris Q Doe

National Institutes of Health (HD27056)

  • Chris Q Doe

National Institutes of Health (T32HD007348)

  • Emily L Heckman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2019, Sales et al.

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.

Metrics

  • 2,841
    views
  • 411
    downloads
  • 19
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Emily C Sales
  2. Emily L Heckman
  3. Timothy L Warren
  4. Chris Q Doe
(2019)
Regulation of subcellular dendritic synapse specificity by axon guidance cues
eLife 8:e43478.
https://doi.org/10.7554/eLife.43478

Share this article

https://doi.org/10.7554/eLife.43478

Further reading

    1. Developmental Biology
    Yanlin Hou, Zhengwen Nie ... Hans R Scholer
    Research Article

    During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 activate the pluripotency-related genes through the putative OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory toward the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.

    1. Developmental Biology
    Yufei Wu, Sean X Sun
    Insight

    Proteins that allow water to move in and out of cells help shape the development of new blood vessels.