1. Developmental Biology
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Mamo decodes hierarchical temporal gradients into terminal neuronal fate

  1. Ling-Yu Liu
  2. Xi Long
  3. Ching-Po Yang
  4. Rosa L Miyares
  5. Ken Sugino
  6. Robert H Singer
  7. Tzumin Lee  Is a corresponding author
  1. Janelia Research Campus, Howard Hughes Medical Institute, United States
  2. Albert Einstein College of Medicine, United States
Research Article
  • Cited 3
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Cite this article as: eLife 2019;8:e48056 doi: 10.7554/eLife.48056

Abstract

Temporal patterning is a seminal method of expanding neuronal diversity. Here we unravel a mechanism decoding neural stem cell temporal gene expression and transforming it into discrete neuronal fates. This mechanism is characterized by hierarchical gene expression. First, Drosophila neuroblasts express opposing temporal gradients of RNA-binding proteins, Imp and Syp. These proteins promote or inhibit chinmo translation, yielding a descending neuronal gradient. Together, first and second-layer temporal factors define a temporal expression window of BTB-zinc finger nuclear protein, Mamo. The precise temporal induction of Mamo is achieved via both transcriptional and post-transcriptional regulation. Finally, Mamo is essential for the temporally defined, terminal identity of α'/β' mushroom body neurons and identity maintenance. We describe a straightforward paradigm of temporal fate specification where diverse neuronal fates are defined via integrating multiple layers of gene regulation. The neurodevelopmental roles of orthologous/related mammalian genes suggest a fundamental conservation of this mechanism in brain development.

Article and author information

Author details

  1. Ling-Yu Liu

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  2. Xi Long

    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:" 0000-0002-0268-8641
  3. Ching-Po Yang

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  4. Rosa L Miyares

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  5. Ken Sugino

    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:" 0000-0002-5795-0635
  6. Robert H Singer

    Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, United States
    Competing interests
    Robert H Singer, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6725-0093
  7. Tzumin Lee

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    leet@janelia.hhmi.org
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0569-0111

Funding

Howard Hughes Medical Institute

  • Tzumin Lee

National Institute of Neurological Disorders and Stroke (NS083085)

  • Robert H Singer

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: April 29, 2019
  2. Accepted: September 20, 2019
  3. Accepted Manuscript published: September 23, 2019 (version 1)
  4. Version of Record published: September 27, 2019 (version 2)

Copyright

© 2019, Liu 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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