The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells
- Southern University of Science and Technology, China
- Chinese Academy of Sciences, China
- Sun Yat-sen University, China
- 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.
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Anti YTHDF2 RIP-seq to identify YTHDF2 target mRNAs in P0 mouse retinasNCBI Gene Expression Omnibus, GSE145390.
Article and author information
Author details
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).
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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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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