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Front Mol Neurosci
2017 Feb 07;10:17. doi: 10.3389/fnmol.2017.00017.
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Gene Expression Profiling in the Injured Spinal Cord of Trachemys scripta elegans: An Amniote with Self-Repair Capabilities.
Valentin-Kahan A
,
García-Tejedor GB
,
Robello C
,
Trujillo-Cenóz O
,
Russo RE
,
Alvarez-Valin F
.
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Slider turtles are the only known amniotes with self-repair mechanisms of the spinal cord that lead to substantial functional recovery. Their strategic phylogenetic position makes them a relevant model to investigate the peculiar genetic programs that allow anatomical reconnection in some vertebrate groups but are absent in others. Here, we analyze the gene expression profile of the response to spinal cord injury (SCI) in the turtle Trachemys scripta elegans. We found that this response comprises more than 1000 genes affecting diverse functions: reaction to ischemic insult, extracellular matrix re-organization, cell proliferation and death, immune response, and inflammation. Genes related to synapses and cholesterol biosynthesis are down-regulated. The analysis of the evolutionary distribution of these genes shows that almost all are present in most vertebrates. Additionally, we failed to find genes that were exclusive of regenerating taxa. The comparison of expression patterns among species shows that the response to SCI in the turtle is more similar to that of mice and non-regenerative Xenopus than to Xenopus during its regenerative stage. This observation, along with the lack of conserved "regeneration genes" and the current accepted phylogenetic placement of turtles (sister group of crocodilians and birds), indicates that the ability of spinal cord self-repair of turtles does not represent the retention of an ancestral vertebrate character. Instead, our results suggest that turtles developed this capability from a non-regenerative ancestor (i.e., a lineage specific innovation) that was achieved by re-organizing gene expression patterns on an essentially non-regenerative genetic background. Among the genes activated by SCI exclusively in turtles, those related to anoxia tolerance, extracellular matrix remodeling, and axonal regrowth are good candidates to underlie functional recovery.
Figure 1. Schematic depiction of the experimental pipeline used to generate an “enriched” C. picta mapping reference and subsequent differential gene expression analysis. Further details in section under the title “de novo transcriptome assembly” and Figures S1–S6 in supplementary file.
Figure 2. Distribution of nucleotide identities between T. scripta and C. picta orthologous sequences.
Figure 3. Gene Ontology enrichment analysis of down-regulated genes. Test set refers to the group of differentially expressed (DE) genes (in this case only down-regulated ones) and reference to all genes in the genome. Only some representative (and informative) terms were included in the figure.
Figure 4. Gene Ontology enrichment analysis of genes that are up-regulated. Symbols as in Figure 3. Panels (A–D) show relevant groups of GO terms. The group of GO categories is indicated at the top of each panel.
Figure 5. Protein Interaction network of T. scripta DE genes. Nodes represent genes and lines interactions. Node colors are used to identify the cluster to which the genes belong to. The most relevant cellular processes and functions associated to each cluster are specified by the legend next to it.
Figure 6. Amino acid identity levels of DE genes in species representative of vertebrate taxonomic diversity. Identity levels are indicated by the color scale shown in the top leftmost corner of figure. Values indicate the identity between T. scripta and the species indicated at the bottom of heatmap. Groups of genes for which no ortholog could be found in a given species are presented in separated panels. (A) Genes that are present all the vertebrate species used in this study. Panels (B–F) show genes absent in a particular species, or clade, as indicated in the sub-title of the respective panel. Genes for which an ortholog could not be unambiguously identified in a given species are indicated in violet.
Figure 7. Comparison of gene expression responses between turtles and mice (i) and turtles vs. NR-Xenopus (ii). Panel (A) genes having double coincident behavior are colored in blue and green (for up- and down-regulated, respectively), whereas those exhibiting opposite responses are colored in red and yellow, for up- and down-regulated respectively. Further details about definitions on gene expression behavior in the text. Groups of genes of interest are boxed with dashed lines and shown in greater magnification in panel (B).
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