1. Developmental Biology

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
https://doi.org/10.7554/eLife.50561
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

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)

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

  • 1,813
    views
  • 254
    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

Categories and tags

Research organism

Further reading

    1. Developmental Biology
    2. Neuroscience

    Volumetric trans-scale imaging of massive quantity of heterogeneous cell populations in centimeter-wide tissue and embryo

    Taro Ichimura, Taishi Kakizuka ... Takeharu Nagai
    Tools and Resources

    We established a volumetric trans-scale imaging system with an ultra-large field-of-view (FOV) that enables simultaneous observation of millions of cellular dynamics in centimeter-wide three-dimensional (3D) tissues and embryos. Using a custom-made giant lens system with a magnification of ×2 and a numerical aperture (NA) of 0.25, and a CMOS camera with more than 100 megapixels, we built a trans-scale scope AMATERAS-2, and realized fluorescence imaging with a transverse spatial resolution of approximately 1.1 µm across an FOV of approximately 1.5×1.0 cm2. The 3D resolving capability was realized through a combination of optical and computational sectioning techniques tailored for our low-power imaging system. We applied the imaging technique to 1.2 cm-wide section of mouse brain, and successfully observed various regions of the brain with sub-cellular resolution in a single FOV. We also performed time-lapse imaging of a 1-cm-wide vascular network during quail embryo development for over 24 hr, visualizing the movement of over 4.0×105 vascular endothelial cells and quantitatively analyzing their dynamics. Our results demonstrate the potential of this technique in accelerating production of comprehensive reference maps of all cells in organisms and tissues, which contributes to understanding developmental processes, brain functions, and pathogenesis of disease, as well as high-throughput quality check of tissues used for transplantation medicine.

    1. Developmental Biology
    2. Evolutionary Biology

    Single-cell sequencing provides clues about the developmental genetic basis of evolutionary adaptations in syngnathid fishes

    Hope M Healey, Hayden B Penn ... William A Cresko
    Research Article

    Seahorses, pipefishes, and seadragons are fishes from the family Syngnathidae that have evolved extraordinary traits including male pregnancy, elongated snouts, loss of teeth, and dermal bony armor. The developmental genetic and cellular changes that led to the evolution of these traits are largely unknown. Recent syngnathid genome assemblies revealed suggestive gene content differences and provided the opportunity for detailed genetic analyses. We created a single-cell RNA sequencing atlas of Gulf pipefish embryos to understand the developmental basis of four traits: derived head shape, toothlessness, dermal armor, and male pregnancy. We completed marker gene analyses, built genetic networks, and examined the spatial expression of select genes. We identified osteochondrogenic mesenchymal cells in the elongating face that express regulatory genes bmp4, sfrp1a, and prdm16. We found no evidence for tooth primordia cells, and we observed re-deployment of osteoblast genetic networks in developing dermal armor. Finally, we found that epidermal cells expressed nutrient processing and environmental sensing genes, potentially relevant for the brooding environment. The examined pipefish evolutionary innovations are composed of recognizable cell types, suggesting that derived features originate from changes within existing gene networks. Future work addressing syngnathid gene networks across multiple stages and species is essential for understanding how the novelties of these fish evolved.

    1. Developmental Biology
    2. Genetics and Genomics

    Genome-wide analysis of Smad and Schnurri transcription factors in C. elegans demonstrates widespread interaction and a function in collagen secretion

    Mehul Vora, Jonathan Dietz ... Cathy Savage-Dunn
    Research Article

    Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands of the transforming growth factor-β (TGF-β) family, including those of the conserved bone morphogenetic protein (BMP) family, yet only a small number of direct target genes have been well characterized. In C. elegans, the BMP2/4 ortholog DBL-1 regulates multiple biological functions, including body size, via a canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad and its transcriptional partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) and expression differences of nearby genes identified from RNA-seq analysis of corresponding mutants. We found that SMA-3 and SMA-9 have both overlapping and unique target genes. At a genome-wide scale, SMA-3/Smad acts as a transcriptional activator, whereas SMA-9/Schnurri direct targets include both activated and repressed genes. Mutations in sma-9 partially suppress the small body size phenotype of sma-3, suggesting some level of antagonism between these factors and challenging the prevailing model for Schnurri function. Functional analysis of target genes revealed a novel role in body size for genes involved in one-carbon metabolism and in the endoplasmic reticulum (ER) secretory pathway, including the disulfide reductase dpy-11. Our findings indicate that Smads and SMA-9/Schnurri have previously unappreciated complex genetic and genomic regulatory interactions that in turn regulate the secretion of extracellular components like collagen into the cuticle to mediate body size regulation.