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XB-ART-57252
BMC Genomics August 5, 2020; 21 (1): 540.

Comparative gene expression profiling between optic nerve and spinal cord injury in Xenopus laevis reveals a core set of genes inherent in successful regeneration of vertebrate central nervous system axons.

Belrose JL , Prasad A , Sammons MA , Gibbs KM , Szaro BG .


Abstract
BACKGROUND: The South African claw-toed frog, Xenopus laevis, is uniquely suited for studying differences between regenerative and non-regenerative responses to CNS injury within the same organism, because some CNS neurons (e.g., retinal ganglion cells after optic nerve crush (ONC)) regenerate axons throughout life, whereas others (e.g., hindbrain neurons after spinal cord injury (SCI)) lose this capacity as tadpoles metamorphose into frogs. Tissues from these CNS regions (frog ONC eye, tadpole SCI hindbrain, frog SCI hindbrain) were used in a three-way RNA-seq study of axotomized CNS axons to identify potential core gene expression programs for successful CNS axon regeneration. RESULTS: Despite tissue-specific changes in expression dominating the injury responses of each tissue, injury-induced changes in gene expression were nonetheless shared between the two axon-regenerative CNS regions that were not shared with the non-regenerative region. These included similar temporal patterns of gene expression and over 300 injury-responsive genes. Many of these genes and their associated cellular functions had previously been associated with injury responses of multiple tissues, both neural and non-neural, from different species, thereby demonstrating deep phylogenetically conserved commonalities between successful CNS axon regeneration and tissue regeneration in general. Further analyses implicated the KEGG adipocytokine signaling pathway, which links leptin with metabolic and gene regulatory pathways, and a novel gene regulatory network with genes regulating chromatin accessibility at its core, as important hubs in the larger network of injury response genes involved in successful CNS axon regeneration. CONCLUSIONS: This study identifies deep, phylogenetically conserved commonalities between CNS axon regeneration and other examples of successful tissue regeneration and provides new targets for studying the molecular underpinnings of successful CNS axon regeneration, as well as a guide for distinguishing pro-regenerative injury-induced changes in gene expression from detrimental ones in mammals.

PubMed ID: 32758133
PMC ID: PMC7430912
Article link: BMC Genomics
Grant support: [+]
Genes referenced: abcb1 acsbg2 aldoa apoe cntrl coq8a cyb5r2 ebf3 enpp2 ezh2 fabp3 fabp7 fads1 fxyd1 hbe1 hes5.1 idh1 irf8 jarid2 kcnn3 kdm7a krt78.5 lep mapk8 mcm6 mex3a ocm1 otop3 pdf pkd2 plp1 prmt1 prph rplp1 slc38a4 slc9a3r2 snrpd3 socs3 sox11 suz12 tf ttl tuba1a tubb2b ugt8 znf395
GO keywords: neural tissue regeneration

GEO Series: GSE137844: NCBI

Article Images: [+] show captions
References [+] :
Abe, Mammalian target of rapamycin (mTOR) activation increases axonal growth capacity of injured peripheral nerves. 2010, Pubmed


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