PUBLICATION
Dtx2 deficiency induces ependymo-radial glial cell proliferation and improves spinal cord motor function recovery
- Authors
- Chen, H.Y., Huang, Y.C., Yeh, T.H., Chang, C.W., Shen, Y.J., Chen, Y.C., Sun, M.Q., Cheng, Y.C.
- ID
- ZDB-PUB-240714-1
- Date
- 2024
- Source
- Stem cells and development 33(19-20): 540-550 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Spinal Cord*/metabolism
- Spinal Cord*/pathology
- Neuroglia/metabolism
- Animals
- Receptors, Notch/genetics
- Receptors, Notch/metabolism
- Spinal Cord Regeneration
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Cell Proliferation*/genetics
- Zebrafish*
- Ependymoglial Cells/cytology
- Ependymoglial Cells/metabolism
- Motor Activity
- Spinal Cord Injuries*/genetics
- Spinal Cord Injuries*/metabolism
- Spinal Cord Injuries*/pathology
- Spinal Cord Injuries*/physiopathology
- Recovery of Function*
- Motor Neurons/metabolism
- Ubiquitin-Protein Ligases/genetics
- Ubiquitin-Protein Ligases/metabolism
- Signal Transduction/genetics
- Mutation/genetics
- PubMed
- 39001828 Full text @ Stem Cells Dev.
Citation
Chen, H.Y., Huang, Y.C., Yeh, T.H., Chang, C.W., Shen, Y.J., Chen, Y.C., Sun, M.Q., Cheng, Y.C. (2024) Dtx2 deficiency induces ependymo-radial glial cell proliferation and improves spinal cord motor function recovery. Stem cells and development. 33(19-20):540-550.
Abstract
Traumatic injury to the spinal cord can lead to significant, permanent disability. Mammalian spinal cords are not capable of regeneration; in contrast, adult zebrafish are capable of such regeneration, fully recovering motor function. Understanding the mechanisms underlying zebrafish neuroregeneration may provide useful information regarding endogenous regenerative potential and aid in the development of therapeutic strategies in humans. DTXs regulate a variety of cellular processes. However, their role in neural regeneration has not been described. We found that zebrafish dtx2, encoding Deltex E3 ubiquitin ligase 2, is expressed in ependymo-radial glial cells in the adult spinal cord. After spinal cord injury, the heterozygous dtx2 mutant fish motor function recovered quicker than that of the wild-type controls. The mutant fish displayed increased ependymo-radial glial cell proliferation and augmented motor neuron formation. Moreover, her gene expression, downstream of Notch signaling, increased in Dtx2 mutants. Notch signaling inactivation by dominant-negative Rbpj abolished the increased ependymo-radial glia proliferation caused by Dtx2 deficiency. These results indicate that ependymo-radial glial proliferation is induced by Dtx2 deficiency, by activating Notch-Rbpj signaling to improve spinal cord regeneration and motor function recovery.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping