MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development

  1. Kanella Prodromidou  Is a corresponding author
  2. Ioannis S Vlachos
  3. Maria Gaitanou
  4. Georgia Kouroupi
  5. Artemis G Hatzigeorgiou
  6. Rebecca Matsas  Is a corresponding author
  1. Hellenic Pasteur Institute, Greece
  2. Beth Israel Deaconess Medical Center, United States
  3. DIANA-Lab, University of Thessaly, Greece

Abstract

Integrating differential RNA and miRNA expression during neuronal lineage induction of human embryonic stem cells we identified miR-934, a primate-specific miRNA that displays a stage-specific expression pattern during progenitor expansion and early neuron generation. We demonstrate the biological relevance of this finding by comparison with data from early to mid-gestation human cortical tissue. Further we find that miR-934 directly controls progenitor to neuroblast transition and impacts on neurite growth of newborn neurons. In agreement, miR-934 targets are involved in progenitor proliferation and neuronal differentiation whilst miR-934 inhibition results in profound global transcriptome changes associated with neurogenesis, axonogenesis, neuronal migration and neurotransmission. Interestingly, miR-934 inhibition affects the expression of genes associated with the subplate zone, a transient compartment most prominent in primates that emerges during early corticogenesis. Our data suggest that mir-934 is a novel regulator of early human neurogenesis with potential implications for a species-specific evolutionary role in brain function.

Data availability

Sequencing data have been deposited in GEO under accession code GSE101548. All data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Kanella Prodromidou

    Neurobiology, Hellenic Pasteur Institute, Athens, Greece
    For correspondence
    kprodromidou@pasteur.gr
    Competing interests
    The authors declare that no competing interests exist.
  2. Ioannis S Vlachos

    Pathology, Beth Israel Deaconess Medical Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maria Gaitanou

    Neurobiology, Hellenic Pasteur Institute, Athens, Greece
    Competing interests
    The authors declare that no competing interests exist.
  4. Georgia Kouroupi

    Neurobiology, Hellenic Pasteur Institute, Athens, Greece
    Competing interests
    The authors declare that no competing interests exist.
  5. Artemis G Hatzigeorgiou

    Department of Electrical & Computer Engineering, DIANA-Lab, University of Thessaly, Volos, Greece
    Competing interests
    The authors declare that no competing interests exist.
  6. Rebecca Matsas

    Neurobiology, Hellenic Pasteur Institute, Athens, Greece
    For correspondence
    rmatsa@pasteur.gr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4027-348X

Funding

Ministry of Education and Religious Affairs, Sport and Culture (Greek General Secreteriat for Research and Technology Grant EXCELLENCE 2272)

  • Rebecca Matsas

Ministry of Education and Religious Affairs, Sport and Culture (Greek General Secreteriat for Research and Technology Grant MIS 5002486)

  • Rebecca Matsas

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

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Ethics

Human subjects: All procedures for generation of human iPSCs were approved by the Scientific Council and Ethics Committee of Attikon University Hospital (Athens, Greece), which is one of the Mendelian forms of Parkinson's Disease clinical centers, and by the Hellenic Pasteur Institute Ethics Committee overlooking stem cell research. Informed consent was obtained from all donors before skin biopsy. Proc Natl Acad Sci U S A. 2017 May 2;114(18)

Version history

  1. Received: July 26, 2019
  2. Accepted: May 21, 2020
  3. Accepted Manuscript published: May 27, 2020 (version 1)
  4. Version of Record published: June 15, 2020 (version 2)

Copyright

© 2020, Prodromidou 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

  • 1,651
    views
  • 243
    downloads
  • 13
    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. Kanella Prodromidou
  2. Ioannis S Vlachos
  3. Maria Gaitanou
  4. Georgia Kouroupi
  5. Artemis G Hatzigeorgiou
  6. Rebecca Matsas
(2020)
MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development
eLife 9:e50561.
https://doi.org/10.7554/eLife.50561

Share this article

https://doi.org/10.7554/eLife.50561

Further reading

    1. Developmental Biology
    Charlotte F Chao, Yanina-Yasmin Pesch ... Elizabeth Rideout
    Research Article

    Drosophila is a powerful model to study how lipids affect spermatogenesis. Yet, the contribution of neutral lipids, a major lipid group which resides in organelles called lipid droplets (LD), to sperm development is largely unknown. Emerging evidence suggests LD are present in the testis and that loss of neutral lipid- and LD-associated genes causes subfertility; however, key regulators of testis neutral lipids and LD remain unclear. Here, we show LD are present in early-stage somatic and germline cells within the Drosophila testis. We identified a role for triglyceride lipase brummer (bmm) in regulating testis LD, and found that whole-body loss of bmm leads to defects in sperm development. Importantly, these represent cell-autonomous roles for bmm in regulating testis LD and spermatogenesis. Because lipidomic analysis of bmm mutants revealed excess triglyceride accumulation, and spermatogenic defects in bmm mutants were rescued by genetically blocking triglyceride synthesis, our data suggest that bmm-mediated regulation of triglyceride influences sperm development. This identifies triglyceride as an important neutral lipid that contributes to Drosophila sperm development, and reveals a key role for bmm in regulating testis triglyceride levels during spermatogenesis.

    1. Developmental Biology
    2. Structural Biology and Molecular Biophysics
    Samuel C Griffiths, Jia Tan ... Hsin-Yi Henry Ho
    Research Article

    The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, Brachydactyly B and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.