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.
Highlights
While traumatic injury to the mammalian central nervous system (CNS) leads to permanent loss of sensory and motor function, many invertebrate and non-mammalian vertebrate species exhibit a remarkable ability to regenerate nervous system structures and recover functionality
The search for conserved molecular pathways that promote neuronal regeneration has led to the identification of activating transcription factor 3 (ATF3) as a potentially critical component
This review highlights its consistent induction during nervous system regeneration across a wide array of vertebrate species, tissue types, and injury models
Summary
While traumatic injury to the mammalian central nervous system (CNS) leads to permanent loss of sensory and motor function, many invertebrate and non-mammalian vertebrate species exhibit a remarkable ability to regenerate nervous system structures and recover functionality. Amongst the RAGs are several conserved transcription factors that activate or de-activate large sets of genes, placing them as hub proteins in a transcriptional regulatory network induced by injury (Chandran et al, 2016) These include activating transcription factor 3 (ATF3) and AP-1 (Fos/Jun), as well as Sox, KLF7, and STAT3 (Moore and Goldberg, 2011; Blackmore et al, 2012; Fagoe et al, 2014; Chandran et al, 2016; Mehta et al, 2016; Fawcett and Verhaagen, 2018; Herman et al, 2018). Given their positions as hubs within the injury-induced gene networks, these transcription factors have potential for being master regulators of neural regeneration, and possibly therapeutic targets
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
