A developmental framework linking neurogenesis and circuit formation in the Drosophila CNS

  1. Brandon Mark
  2. Sen-Lin Lai
  3. Aref Arzan Zarin
  4. Laurina Manning
  5. Heather Q Pollington
  6. Ashok Litwin-Kumar
  7. Albert Cardona
  8. James W Truman
  9. Chris Q Doe  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Oregon, United States
  2. Howard Hughes Medical Institute, University of Oregonof Oregon, United States
  3. Columbia University, United States
  4. University of Cambridge, United Kingdom
  5. Janelia Research Campus, Howard Hughes Medical Institute, United States

Abstract

The mechanisms specifying neuronal diversity are well-characterized, yet it remains unclear how or if these mechanisms regulate neural circuit assembly. To address this, we mapped the developmental origin of 160 interneurons from seven bilateral neural progenitors (neuroblasts), and identify them in a synapse-scale TEM reconstruction of the Drosophila larval CNS. We find that lineages concurrently build the sensory and motor neuropils by generating sensory and motor hemilineages in a Notch-dependent manner. Neurons in a hemilineage share common synaptic targeting within the neuropil, which is further refined based on neuronal temporal identity. Connectome analysis shows that hemilineage-temporal cohorts share common connectivity. Finally, we show that proximity alone cannot explain the observed connectivity structure, suggesting hemilineage/temporal identity confers an added layer of specificity. Thus, we demonstrate that the mechanisms specifying neuronal diversity also govern circuit formation and function, and that these principles are broadly applicable throughout the nervous system.

Data availability

All data are publicly available from https://github.com/bjm5164/Mark2020_larval_development.

Article and author information

Author details

  1. Brandon Mark

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    No competing interests declared.
  2. Sen-Lin Lai

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7531-283X
  3. Aref Arzan Zarin

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0484-3622
  4. Laurina Manning

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregonof Oregon, Eugene, United States
    Competing interests
    No competing interests declared.
  5. Heather Q Pollington

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    Competing interests
    No competing interests declared.
  6. Ashok Litwin-Kumar

    Department of Neuroscience, Columbia University, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2422-6576
  7. Albert Cardona

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    Albert Cardona, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4941-6536
  8. James W Truman

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9209-5435
  9. Chris Q Doe

    Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States
    For correspondence
    cdoe@uoregon.edu
    Competing interests
    Chris Q Doe, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5980-8029

Funding

NIH (HD27056)

  • Brandon Mark
  • Sen-Lin Lai
  • Aref Arzan Zarin
  • Laurina Manning
  • Heather Q Pollington
  • Chris Q Doe

HHMI

  • Brandon Mark
  • Sen-Lin Lai
  • Aref Arzan Zarin
  • Laurina Manning
  • Heather Q Pollington
  • Chris Q Doe

HHMI - Janelia Research Campus

  • Albert Cardona
  • James W Truman

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

Reviewing Editor

  1. Claude Desplan, New York University, United States

Publication history

  1. Received: February 12, 2021
  2. Accepted: May 10, 2021
  3. Accepted Manuscript published: May 11, 2021 (version 1)
  4. Version of Record published: May 21, 2021 (version 2)
  5. Version of Record updated: June 15, 2021 (version 3)

Copyright

© 2021, Mark 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.

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  1. Brandon Mark
  2. Sen-Lin Lai
  3. Aref Arzan Zarin
  4. Laurina Manning
  5. Heather Q Pollington
  6. Ashok Litwin-Kumar
  7. Albert Cardona
  8. James W Truman
  9. Chris Q Doe
(2021)
A developmental framework linking neurogenesis and circuit formation in the Drosophila CNS
eLife 10:e67510.
https://doi.org/10.7554/eLife.67510

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