The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells

  1. Fugui Niu
  2. Peng Han
  3. Jian Zhang
  4. Yuanchu She
  5. Lixin Yang
  6. Jun Yu
  7. Mengru Zhuang
  8. Kezhen Tang
  9. Yuwei Shi
  10. Baisheng Yang
  11. Chunqiao Liu
  12. Bo Peng  Is a corresponding author
  13. Sheng-Jian Ji  Is a corresponding author
  1. Southern University of Science and Technology, China
  2. Chinese Academy of Sciences, China
  3. Sun Yat-sen University, China
  4. Fudan University, China

Abstract

The precise control of growth and maintenance of the retinal ganglion cell (RGC) dendrite arborization is critical for normal visual functions in mammals. However, the underlying mechanisms remain elusive. Here we find that the m6A reader YTHDF2 is highly expressed in the mouse RGCs. Conditional knockout (cKO) of Ythdf2 in the retina leads to increased RGC dendrite branching, resulting in more synapses in the inner plexiform layer. Interestingly, the Ythdf2 cKO mice show improved visual acuity compared with control mice. We further demonstrate that Ythdf2 cKO in the retina protects RGCs from dendrite degeneration caused by the experimental acute glaucoma model. We identify the m6A-modified YTHDF2 target transcripts which mediate these effects. This study reveals mechanisms by which YTHDF2 restricts RGC dendrite development and maintenance. YTHDF2 and its target mRNAs might be valuable in developing new treatment approaches for glaucomatous eyes.

Data availability

The RIP-seq data have been deposited to the Gene Expression Omnibus (GEO) with accession number GSE145390. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD017775.

The following data sets were generated

Article and author information

Author details

  1. Fugui Niu

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Peng Han

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Jian Zhang

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuanchu She

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Lixin Yang

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jun Yu

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Mengru Zhuang

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Kezhen Tang

    Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yuwei Shi

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Baisheng Yang

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Chunqiao Liu

    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Bo Peng

    Department of Neurosurgery, Fudan University, Shanghai, China
    For correspondence
    peng@fudan.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4183-5939
  13. Sheng-Jian Ji

    Department of Biology, Southern University of Science and Technology, Shenzhen, China
    For correspondence
    jisj@sustech.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3380-258X

Funding

National Natural Science Foundation of China (31871038)

  • Sheng-Jian Ji

National Natural Science Foundation of China (32170955)

  • Sheng-Jian Ji

National Natural Science Foundation of China (31922027)

  • Bo Peng

National Natural Science Foundation of China (32170958)

  • Bo Peng

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

Ethics

Animal experimentation: All experiments using mice were carried out following the animal protocols approved by the Laboratory Animal Welfare and Ethics Committee of Southern University of Science and Technology (approval numbers: SUSTC-JY2017004, SUSTC-JY2019081).

Reviewing Editor

  1. Carol A Mason, Columbia University, United States

Publication history

  1. Received: November 24, 2021
  2. Preprint posted: December 7, 2021 (view preprint)
  3. Accepted: February 16, 2022
  4. Accepted Manuscript published: February 18, 2022 (version 1)
  5. Version of Record published: March 9, 2022 (version 2)
  6. Version of Record updated: March 14, 2022 (version 3)
  7. Version of Record updated: April 4, 2022 (version 4)

Copyright

© 2022, Niu 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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  1. Fugui Niu
  2. Peng Han
  3. Jian Zhang
  4. Yuanchu She
  5. Lixin Yang
  6. Jun Yu
  7. Mengru Zhuang
  8. Kezhen Tang
  9. Yuwei Shi
  10. Baisheng Yang
  11. Chunqiao Liu
  12. Bo Peng
  13. Sheng-Jian Ji
(2022)
The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells
eLife 11:e75827.
https://doi.org/10.7554/eLife.75827

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