The m<sup>6</sup>A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35179492.
- Also identified by DOI 10.7554/eLife.75827 and PMC identifier 8906807.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) reader YTHDF2 is highly expressed in the mouse RGCs. Conditional knockout (cKO) of <i>Ythdf2</i> in the retina leads to increased RGC dendrite branching, resulting in more synapses in the inner plexiform layer. Interestingly, the <i>Ythdf2</i> cKO mice show improved visual acuity compared with control mice. We further demonstrate that <i>Ythdf2</i> cKO in the retina protects RGCs from dendrite degeneration caused by the experimental acute glaucoma model. We identify the m<sup>6</sup>A-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.
Medical subject headings
- Glaucoma
- Retinal Ganglion Cells