Sequential addition of neuronal stem cell temporal cohorts generates a feed-forward circuit in the Drosophila larval nerve cord

Abstract

How circuits self-assemble starting from neuronal stem cells is a fundamental question in developmental neurobiology. Here, we addressed how neurons from different stem cell lineages wire with each other to form a specific circuit motif. In Drosophila larvae, we combined developmental genetics (Twin spot MARCM, Multi-color Flip Out, permanent labeling) with circuit analysis (calcium imaging, connectomics, network science). For many lineages, neuronal progeny are organized into subunits called temporal cohorts. Temporal cohorts are subsets of neurons born within a tight time window that have shared circuit level function. We find sharp transitions in patterns of input connectivity at temporal cohort boundaries. In addition, we identify a feed-forward circuit that encodes the onset of vibration stimuli. This feed-forward circuit is assembled by preferential connectivity between temporal cohorts from different lineages. Connectivity does not follow the often-cited early-to-early, late-to-late model. Instead, the circuit is formed by sequential addition of temporal cohorts from different lineages, with circuit output neurons born before circuit input neurons. Further, we generate new tools for the fly community. Our data raise the possibility that sequential addition of neurons (with outputs oldest and inputs youngest) could be one fundamental strategy for assembling feed-forward circuits.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files (Supplemental Tables 1-6)Source Data files are provided for Figures 3,4,5,6,7,9,10.13.14

Article and author information

Author details

  1. Yi-wen Wang

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Chris C Wreden

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maayan Levy

    Committee on Computational Neuroscience, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Julia L Meng

    Program in Cell and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zarion D Marshall

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jason MacLean

    Committee on Computational Neuroscience, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Ellie Heckscher

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    For correspondence
    heckscher@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7618-0616

Funding

National Institute of Neurological Disorders and Stroke (NS105748)

  • Ellie Heckscher

National Eye Institute (EY022338)

  • Jason MacLean

Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32 HD044164)

  • Zarion D Marshall

National Science Foundation (DGE-1746045)

  • Julia L Meng

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

Reviewing Editor

  1. P Robin Hiesinger, Institute for Biology Free University Berlin, Germany

Version history

  1. Preprint posted: April 6, 2022 (view preprint)
  2. Received: April 6, 2022
  3. Accepted: June 17, 2022
  4. Accepted Manuscript published: June 20, 2022 (version 1)
  5. Version of Record published: July 28, 2022 (version 2)

Copyright

© 2022, Wang 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. Yi-wen Wang
  2. Chris C Wreden
  3. Maayan Levy
  4. Julia L Meng
  5. Zarion D Marshall
  6. Jason MacLean
  7. Ellie Heckscher
(2022)
Sequential addition of neuronal stem cell temporal cohorts generates a feed-forward circuit in the Drosophila larval nerve cord
eLife 11:e79276.
https://doi.org/10.7554/eLife.79276

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https://doi.org/10.7554/eLife.79276

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