Activating transcription factor 3 (ATF3) is a highly conserved pro-regenerative transcription factor in the vertebrate nervous system
Activating transcription factor 3 (ATF3) is a highly conserved pro-regenerative transcription factor in the vertebrate nervous system
Date
2022-03-08
Authors
Katz, Hilary R.
Arcese, Anthony A.
Bloom, Ona E.
Morgan, Jennifer R.
Arcese, Anthony A.
Bloom, Ona E.
Morgan, Jennifer R.
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DOI
10.3389/fcell.2022.824036
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Keywords
Regeneration
Spinal cord injury
Zebrafish
Lamprey
Dorsal root ganglia (DRG) neurons
Spinal cord injury
Zebrafish
Lamprey
Dorsal root ganglia (DRG) neurons
Abstract
The vertebrate nervous system exhibits dramatic variability in regenerative capacity across species and neuronal populations. For example, while the mammalian central nervous system (CNS) is limited in its regenerative capacity, the CNS of many other vertebrates readily regenerates after injury, as does the peripheral nervous system (PNS) of mammals. Comparing molecular responses across species and tissues can therefore provide valuable insights into both conserved and distinct mechanisms of successful regeneration. One gene that is emerging as a conserved pro-regenerative factor across vertebrates is activating transcription factor 3 (ATF3), which has long been associated with tissue trauma. A growing number of studies indicate that ATF3 may actively promote neuronal axon regrowth and regeneration in species ranging from lampreys to mammals. Here, we review data on the structural and functional conservation of ATF3 protein across species. Comparing RNA expression data across species that exhibit different abilities to regenerate their nervous system following traumatic nerve injury reveals that ATF3 is consistently induced in neurons within the first few days after injury. Genetic deletion or knockdown of ATF3 expression has been shown in mouse and zebrafish, respectively, to reduce axon regeneration, while inducing ATF3 promotes axon sprouting, regrowth, or regeneration. Thus, we propose that ATF3 may be an evolutionarily conserved regulator of neuronal regeneration. Identifying downstream effectors of ATF3 will be a critical next step in understanding the molecular basis of vertebrate CNS regeneration.
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© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Katz, H. R., Arcese, A. A., Bloom, O., & Morgan, J. R. Activating transcription factor 3 (ATF3) is a highly conserved pro-regenerative transcription factor in the vertebrate nervous system. Frontiers in Cell and Developmental Biology, 10, (2022): 824036, https://doi.org/10.3389/fcell.2022.824036.
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Katz, H. R., Arcese, A. A., Bloom, O., & Morgan, J. R. (2022). Activating transcription factor 3 (ATF3) is a highly conserved pro-regenerative transcription factor in the vertebrate nervous system. Frontiers in Cell and Developmental Biology, 10, 824036.