Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (1): 103-111.doi: 10.4103/1673-5374.264460

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Bioinformatic identification of key candidate genes and pathways in axon regeneration after spinal cord injury in zebrafish

Jia-He Li1, Zhong-Ju Shi1, Yan Li1, Bin Pan2, Shi-Yang Yuan1, Lin-Lin Shi1,Yan Hao1, Fu-Jiang Cao1, Shi-Qing Feng1, 3   

  1. 1 Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China
    2 Department of Orthopedics, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
    3 Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
  • Online:2020-01-15 Published:2020-05-20
  • Contact: Shi-Qing Feng, PhD,sqfeng@tmu.edu.cn.
  • Supported by:
    This work was supported by the State Key Program of National Natural Science Foundation of China, No. 81330042 (to SQF); the
    International Cooperation Program of the National Natural Science Foundation of China, No. 81620108018 (to SQF).

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Abstract: Zebrafish and human genomes are highly homologous; however, despite this genomic similarity, adult zebrafish can achieve neuronal proliferation, regeneration and functional restoration within 6–8 weeks after spinal cord injury, whereas humans cannot. To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury, and to explore the key genes and pathways of axonal regeneration after spinal cord injury, microarray GSE56842 was analyzed using the online tool, GEO2R, in the Gene Expression Omnibus database. Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes. Finally, we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals. A total of 636 differentially expressed genes were obtained, including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained. A protein-protein interaction network contained 480 node genes and 1976 node connections. We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score. The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish. Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish. Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells, such as Schwann cells or neural progenitor cells, after spinal cord injury in zebrafish. Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish, providing targets for treatment of spinal cord injury in mammals.

Key words: axonal regeneration, differentially expressed genes, focal adhesions, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes,
neural regeneration, protein-protein interaction network, signaling pathway, spectrin, tight junctions, transforming growth factor beta, Wnt signaling pathway