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

Version 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.

Metrics

  • 2,699
    views
  • 393
    downloads
  • 45
    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. 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

Share this article

https://doi.org/10.7554/eLife.67510

Further reading

    1. Chromosomes and Gene Expression
    2. Developmental Biology
    F Javier DeHaro-Arbona, Charalambos Roussos ... Sarah Bray
    Research Article

    Developmental programming involves the accurate conversion of signalling levels and dynamics to transcriptional outputs. The transcriptional relay in the Notch pathway relies on nuclear complexes containing the co-activator Mastermind (Mam). By tracking these complexes in real time, we reveal that they promote the formation of a dynamic transcription hub in Notch ON nuclei which concentrates key factors including the Mediator CDK module. The composition of the hub is labile and persists after Notch withdrawal conferring a memory that enables rapid reformation. Surprisingly, only a third of Notch ON hubs progress to a state with nascent transcription, which correlates with polymerase II and core Mediator recruitment. This probability is increased by a second signal. The discovery that target-gene transcription is probabilistic has far-reaching implications because it implies that stochastic differences in Notch pathway output can arise downstream of receptor activation.

    1. Developmental Biology
    Rieko Asai, Vivek N Prakash ... Takashi Mikawa
    Research Article

    Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.