title: E2F4 Promotes Neuronal Regeneration and Functional Recovery after Spinal Cord Injury in Zebrafish.
abstract: Mammals exhibit poor recovery after spinal cord injury (SCI), whereas non-mammalian vertebrates exhibit significant spontaneous recovery after SCI. The mechanisms underlying this difference have not been fully elucidated; therefore, the purpose of this study was to investigate these mechanisms. Using comparative transcriptome analysis, we demonstrated that genes related to cell cycle were significantly enriched in the genes specifically dysregulated in zebrafish SCI. Most of the cell cycle-related genes dysregulated in zebrafish SCI were down-regulated, possibly through activation of e2f4. Using a larval zebrafish model of SCI, we demonstrated that the recovery of locomotive function and neuronal regeneration after SCI were significantly inhibited in zebrafish treated with an E2F4 inhibitor. These results suggest that activation of e2f4 after SCI may be responsible, at least in part, for the significant recovery in zebrafish. This provides novel insight into the lack of recovery after SCI in mammals and informs potential therapeutic strategies.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Sasagawa
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of MedicineTsu, Japan; Mie University Medical Zebrafish Research CenterTsu, Japan; Department of Systems Pharmacology, Mie University Graduate School of MedicineTsu, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation InstituteTsu, Japan; Department of Bioinformatics, Mie University Life Science Research CenterTsu, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hayakawa
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ashikawa
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Yuge
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Shiko
authors.initials: S
authors.lastname: Okabe
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kawase
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of MedicineTsu, Japan; Mie University Medical Zebrafish Research CenterTsu, Japan; Department of Systems Pharmacology, Mie University Graduate School of MedicineTsu, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation InstituteTsu, Japan; Department of Bioinformatics, Mie University Life Science Research CenterTsu, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
keywords: DREAM complex; E2F4; comparative transcriptome analysis; spinal cord injury; systems pharmacology; zebrafish