1. Developmental Biology
  2. Neuroscience
Download icon

How prolonged expression of Hb, a temporal transcription factor, re-wires locomotor circuits

  1. Julia L Meng
  2. Zarion D Marshall
  3. Meike Lobb-Rabe
  4. Ellie S Heckscher  Is a corresponding author
  1. University of Chicago, United States
Research Article
  • Cited 9
  • Views 1,743
  • Annotations
Cite this article as: eLife 2019;8:e46089 doi: 10.7554/eLife.46089

Abstract

How circuits assemble starting from stem cells is a fundamental question in developmental neurobiology. We test the hypothesis that, in neuronal stem cells, temporal transcription factors predictably control neuronal terminal features and circuit assembly. Using the Drosophila motor system, we manipulate expression of the classic temporal transcription factor, Hunchback (Hb) specifically in the NB7-1 stem cell, which produces U motor neurons (MNs), and then we monitor dendrite morphology and neuromuscular synaptic partnerships. We find that prolonged expression of Hb leads to transient specification of U MN identity, and that embryonic molecular markers do not accurately predict U MN terminal features. Nonetheless, our data show Hb acts as a potent regulator of neuromuscular wiring decisions. These data introduce important refinements to current models, show that molecular information acting early in neurogenesis as a switch to control motor circuit wiring and provide novel insight into the relationship between stem cell and circuit.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Julia L Meng

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. 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.
  3. Meike Lobb-Rabe

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ellie S 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 (R01-NS105748)

  • Ellie S Heckscher

National Institute of General Medical Sciences (T32 GM007183)

  • Julia L Meng

National Science Foundation (DGE-1746045)

  • Julia L Meng

University of Chicago

  • Ellie S Heckscher

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

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: February 14, 2019
  2. Accepted: September 9, 2019
  3. Accepted Manuscript published: September 10, 2019 (version 1)
  4. Version of Record published: September 20, 2019 (version 2)

Copyright

© 2019, Meng 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

  • 1,743
    Page views
  • 187
    Downloads
  • 9
    Citations

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

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. Developmental Biology
    2. Neuroscience
    Nishtha Ranawat, Ichiro Masai
    Research Article

    Microglia are brain-resident macrophages that function as the first line of defense in brain. Embryonic microglial precursors originate in peripheral mesoderm and migrate into the brain during development. However, the mechanism by which they colonize the brain is incompletely understood. The retina is one of the first brain regions to accommodate microglia. In zebrafish, embryonic microglial precursors use intraocular hyaloid blood vessels as a pathway to migrate into the optic cup via the choroid fissure. Once retinal progenitor cells exit the cell cycle, microglial precursors associated with hyaloid blood vessels start to infiltrate the retina preferentially through neurogenic regions, suggesting that colonization of retinal tissue depends upon the neurogenic state. Along with blood vessels and retinal neurogenesis, IL34 also participates in microglial precursor colonization of the retina. Altogether, CSF receptor signaling, blood vessels, and neuronal differentiation function as cues to create an essential path for microglial migration into developing retina.

    1. Developmental Biology
    Ali Seleit et al.
    Research Article

    The CRISPR/Cas9 system has been used to generate fluorescently labelled fusion proteins by homology directed repair in a variety of species. Despite its revolutionary success, there remains an urgent need for increased simplicity and efficiency of genome editing in research organisms. Here, we establish a simplified, highly efficient and precise strategy for CRISPR/Cas9 mediated endogenous protein tagging in medaka (Oryzias latipes). We use a cloning-free approach that relies on PCR amplified donor fragments containing the fluorescent reporter sequences flanked by short homology arms (30-40bp), a synthetic sgRNA and Cas9 mRNA. We generate eight novel knock-in lines with high efficiency of F0 targeting and germline transmission. Whole Genome Sequencing (WGS) results reveal single-copy integration events only at the targeted loci. We provide an initial characterization of these fusion-protein lines, significantly expanding the repertoire of genetic tools available in medaka. In particular, we show that the mScarlet-pcna line has the potential to serve as an organismal-wide label for proliferative zones and an endogenous cell cycle reporter.