|ZFIN ID: ZDB-PUB-200804-7|
Copper Stress Induces Zebrafish Central Neural System Myelin Defects via WNT/NOTCH-hoxb5b Signaling and pou3f1/fam168a/fam168b DNA Methylation
Zhang, T., Guan, P., Liu, W., Zhao, G., Fang, Y., Fu, H., Gui, J.F., Li, G., Liu, J.X.
|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|
|PubMed:||32745624 Full text @ BBA Gene Regulatory Mechanisms|
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.
ABSTRACTUnbalanced 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.