Document Type
Article
Publication Date
4-15-2023
Original Citation
Rheaume B,
Xing J,
Lukomska A,
Theune W,
Damania A,
Sjogren G,
Trakhtenberg E.
Pten inhibition dedifferentiates long-distance axon-regenerating intrinsically photosensitive retinal ganglion cells and upregulates mitochondria-associated Dynlt1a and Lars2. Development. 2023;150(8).
Keywords
JGM, SS1, Amino Acyl-tRNA Synthetases, Axons, Mitochondria, Nerve Regeneration, Optic Nerve Injuries, PTEN Phosphohydrolase, Retinal Ganglion Cells
JAX Source
Development. 2023;150(8).
ISSN
1477-9129
PMID
37039265
DOI
https://doi.org/10.1242/dev.201644
Grant
This work was supported by grants from The School of Medicine, University of Connecticut, Start-Up Funds (to E.F.T.), and the National Institutes of Health (grant R01-EY029739, to E.F.T.). Open access funding provided by National Institutes of Health. Deposited in PMC for immediate release.
Abstract
Central nervous system projection neurons fail to spontaneously regenerate injured axons. Targeting developmentally regulated genes in order to reactivate embryonic intrinsic axon growth capacity or targeting pro-growth tumor suppressor genes such as Pten promotes long-distance axon regeneration in only a small subset of injured retinal ganglion cells (RGCs), despite many RGCs regenerating short-distance axons. A recent study identified αRGCs as the primary type that regenerates short-distance axons in response to Pten inhibition, but the rare types which regenerate long-distance axons, and cellular features that enable such response, remained unknown. Here, we used a new method for capturing specifically the rare long-distance axon-regenerating RGCs, and also compared their transcriptomes with embryonic RGCs, in order to answer these questions. We found the existence of adult non-α intrinsically photosensitive M1 RGC subtypes that retained features of embryonic cell state, and showed that these subtypes partially dedifferentiated towards an embryonic state and regenerated long-distance axons in response to Pten inhibition. We also identified Pten inhibition-upregulated mitochondria-associated genes, Dynlt1a and Lars2, which promote axon regeneration on their own, and thus present novel therapeutic targets.
Comments
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed