Down-Regulation of hspb9 and hspb11 Contributes to Wavy Notochord in Zebrafish Embryos Following Exposure to Polychlorinated Diphenylsulfides
It is hypothesized that key genes, other than ahr2, are present and associated with the development of a unique type of notochord malformation known as wavy notochord in early life stages of zebrafish following exposure to polychlorinated diphenylsulfides (PCDPSs). To investigate the potential mechanism(s), time-dependent developmental morphologies of zebrafish embryos following exposure to 2500 nM 2,4,4′,5-tetra-CDPS, 2,2′,4-tri-CDPS or 4,4′-di-CDPS were observed to determine the developmental time point when notochord twists began to occur (i.e., 21 h-postfertilization (hpf)). Simultaneously, morphometric measurements suggested that PCDPS exposure did not affect notochord growth at 21 or 120 hpf; however, elongation of the body axis was significantly inhibited at 120 hpf. Transcriptome analysis revealed that the retardation of body growth was potentially related with dysregulation of transcripts predominantly associated with the insulin-associated Irs-Akt-FoxO cascade. Moreover, knockdown and gain-of-function experiments in vivo on codifferentially expressed genes demonstrated that reduced expression of hspb9 and hspb11 contributed to the occurrence of wavy notochord. The results of this study strongly support the hypothesis that the notochord kinks and twists are triggered by the down-regulation of hspb9 and hspb11, and intensified by body growth retardation along with normal notochord length in PCDPS-exposed zebrafish embryos.
|Journal||Environmental Science and Technology|
Zhang, R. (Rui), Wang, X. (Xiaoxiang), Zhang, X. (Xuesheng), Zhang, J. (Junjiang), Zhang, X. (Xiaowei), Shi, X. (Xiao), … Liu, C. (Chunsheng). (2018). Down-Regulation of hspb9 and hspb11 Contributes to Wavy Notochord in Zebrafish Embryos Following Exposure to Polychlorinated Diphenylsulfides. Environmental Science and Technology. doi:10.1021/acs.est.8b04487