PUBLICATION
Copper Stress Induces Zebrafish Central Neural System Myelin Defects via WNT/NOTCH-hoxb5b Signaling and pou3f1/fam168a/fam168b DNA Methylation
- Authors
- Zhang, T., Guan, P., Liu, W., Zhao, G., Fang, Y., Fu, H., Gui, J.F., Li, G., Liu, J.X.
- ID
- ZDB-PUB-200804-7
- Date
- 2020
- Source
- Biochimica et biophysica acta. Gene regulatory mechanisms 1863(10): 194612 (Journal)
- Registered Authors
- Gui, Jian-Fang, Liu, Jing-xia, Zhang, Ting
- Keywords
- DNA methylation, copper, fam168b/pou3f1, hoxb5b, myelin
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Axons/metabolism
- Copper/adverse effects
- Copper/metabolism*
- DNA Methylation*
- Embryonic Development/genetics
- Gain of Function Mutation
- Gene Expression Regulation, Developmental
- Loss of Function Mutation
- Myelin Sheath/genetics*
- Myelin Sheath/metabolism*
- Receptors, Notch/metabolism
- Signal Transduction
- Stress, Physiological*
- Wnt Proteins/metabolism
- Zebrafish/genetics*
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 32745624 Full text @ BBA Gene Regulatory Mechanisms
Citation
Zhang, T., Guan, P., Liu, W., Zhao, G., Fang, Y., Fu, H., Gui, J.F., Li, G., Liu, J.X. (2020) Copper Stress Induces Zebrafish Central Neural System Myelin Defects via WNT/NOTCH-hoxb5b Signaling and pou3f1/fam168a/fam168b DNA Methylation. Biochimica et biophysica acta. Gene regulatory mechanisms. 1863(10):194612.
Abstract
Unbalanced copper (Cu) homeostasis is associated with neurological development defects and diseases. However, the molecular mechanisms remain elusive. Here, central neural system (CNS) myelin defects and the down-regulated expression of WNT/NOTCH signaling and its down-stream mediator hoxb5b were observed in Cu2+ stressed zebrafish larvae. The loss/knockdown-of-function of hoxb5b phenocopied the myelin and axon defects observed in Cu2+ stressed embryos. Meanwhile, the activation of WNT/NOTCH signaling and ectopic expression of hoxb5b could rescue Cu induced myelin defects. Additionally, fam168b, similar to pou3f1/2, exhibited significant promoter hypermethylation and reduced expression in Cu2+ stressed embryos. The hypermethylated locus in fam168b promoter acted pivotally in its transcription, and the loss/knockdown of fam168b/pou3f1 also induced myelin defects. This study also demonstrated that fam168b/pou3f1 and hoxb5b axis acted in a seesaw manner during fish embryogenesis: Cu induced the down-regulated expression of the WNT&NOTCH-hoxb5b axis through the function of copper transporter cox17, coupled with the promoter methylation of genes fam168b/pou3f1, and its subsequent down-regulated expression through the function of another transporter atp7b, making joint contributions to myelin defects in embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping