1. Neuroscience
Download icon

Brain-wide cellular resolution imaging of Cre transgenic zebrafish lines for functional circuit-mapping

  1. Kathryn M Tabor
  2. Gregory D Marquart
  3. Christopher Hurt
  4. Trevor S Smith
  5. Alexandra K Geoca
  6. Ashwin A Bhandiwad
  7. Abhignya Subedi
  8. Jennifer L Sinclair
  9. Hannah M Rose
  10. Nicholas F Polys
  11. Harold A Burgess  Is a corresponding author
  1. National Institute of Child Health and Human Development, United States
  2. Virginia Polytechnic Institute and State University, United States
Tools and Resources
  • Cited 8
  • Views 2,807
  • Annotations
Cite this article as: eLife 2019;8:e42687 doi: 10.7554/eLife.42687

Abstract

Decoding the functional connectivity of the nervous system is facilitated by transgenic methods that express a genetically encoded reporter or effector in specific neurons; however, most transgenic lines show broad spatiotemporal and cell-type expression. Increased specificity can be achieved using intersectional genetic methods which restrict reporter expression to cells that co-express multiple drivers, such as Gal4 and Cre. To facilitate intersectional targeting in zebrafish, we have generated more than 50 new Cre lines, and co-registered brain expression images with the Zebrafish Brain Browser, a cellular resolution atlas of 264 transgenic lines. Lines labeling neurons of interest can be identified using a web-browser to perform a 3D spatial search (zbbrowser.com). This resource facilitates the design of intersectional genetic experiments and will advance a wide range of precision circuit-mapping studies.

Article and author information

Author details

  1. Kathryn M Tabor

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Gregory D Marquart

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9811-5372
  3. Christopher Hurt

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Trevor S Smith

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alexandra K Geoca

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ashwin A Bhandiwad

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Abhignya Subedi

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jennifer L Sinclair

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Hannah M Rose

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nicholas F Polys

    Department of Computer Science, Virginia Polytechnic Institute and State University, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Harold A Burgess

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    For correspondence
    burgessha@mail.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1966-7801

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (1ZIAHD008884-04)

  • Harold A Burgess

Virginia Tech Advanced Research Computing (NA)

  • Nicholas F Polys

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#15-039) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Reviewing Editor

  1. Indira M Raman, Northwestern University, United States

Publication history

  1. Received: October 8, 2018
  2. Accepted: February 7, 2019
  3. Accepted Manuscript published: February 8, 2019 (version 1)
  4. Version of Record published: February 27, 2019 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,807
    Page views
  • 438
    Downloads
  • 8
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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)

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

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

Further reading

    1. Neuroscience
    Lihong Zhan et al.
    Research Article Updated

    Microglia are the resident myeloid cells in the central nervous system (CNS). The majority of microglia rely on CSF1R signaling for survival. However, a small subset of microglia in mouse brains can survive without CSF1R signaling and reestablish the microglial homeostatic population after CSF1R signaling returns. Using single-cell transcriptomic analysis, we characterized the heterogeneous microglial populations under CSF1R inhibition, including microglia with reduced homeostatic markers and elevated markers of inflammatory chemokines and proliferation. Importantly, MAC2/Lgals3 was upregulated under CSF1R inhibition, and shared striking similarities with microglial progenitors in the yolk sac and immature microglia in early embryos. Lineage-tracing studies revealed that these MAC2+ cells were of microglial origin. MAC2+ microglia were also present in non-treated adult mouse brains and exhibited immature transcriptomic signatures indistinguishable from those that survived CSF1R inhibition, supporting the notion that MAC2+ progenitor-like cells are present among adult microglia.

    1. Developmental Biology
    2. Neuroscience
    Yasmine Cantaut-Belarif et al.
    Research Article Updated

    The cerebrospinal fluid (CSF) contains an extracellular thread conserved in vertebrates, the Reissner fiber, which controls body axis morphogenesis in the zebrafish embryo. Yet, the signaling cascade originating from this fiber to ensure body axis straightening is not understood. Here, we explore the functional link between the Reissner fiber and undifferentiated spinal neurons contacting the CSF (CSF-cNs). First, we show that the Reissner fiber is required in vivo for the expression of urp2, a neuropeptide expressed in CSF-cNs. We show that the Reissner fiber is also required for embryonic calcium transients in these spinal neurons. Finally, we study how local adrenergic activation can substitute for the Reissner fiber-signaling pathway to CSF-cNs and rescue body axis morphogenesis. Our results show that the Reissner fiber acts on CSF-cNs and thereby contributes to establish body axis morphogenesis, and suggest it does so by controlling the availability of a chemical signal in the CSF.