PUBLICATION

Proapoptotic Bad Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish

Authors
Hung, J.C., Wu, J.L., Hong, J.R.
ID
ZDB-PUB-210603-2
Date
2021
Source
International Journal of Molecular Sciences   22(9): (Journal)
Registered Authors
Hong, Jiann-Ruey, Wu, Jen-Leih
Keywords
bad, brain defect, environmental stress, gene knockdown, p53/caspase-8 death signaling
MeSH Terms
  • Animals
  • Apoptosis
  • Brain/embryology*
  • Brain/growth & development*
  • Brain/pathology
  • Embryonic Development*/genetics
  • Gene Expression Regulation, Developmental
  • Genes, p53
  • Morpholinos/metabolism
  • Reactive Oxygen Species/metabolism
  • Signal Transduction
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • bcl-Associated Death Protein/genetics
  • bcl-Associated Death Protein/metabolism*
PubMed
34063300 Full text @ Int. J. Mol. Sci.
Abstract
The BH3-only molecule Bad regulates cell death via its differential protein phosphorylation, but very few studies address its effect on early embryonic development in vertebrate systems. In this work, we examined the novel role of zebrafish Bad in the initial programmed cell death (PCD) for brain morphogenesis through reducing environmental stress and cell death signaling. Bad was considered to be a material factor that because of the knockdown of Bad by morpholino oligonucleotides, PCD was increased and the reactive oxygen species (ROS) level was enhanced, which correlated to trigger a p53/caspase-8 involving cell death signaling. This Bad knockdown-mediated environmental stress and enhanced cell dying can delay normal cell migration in the formation of the three germ layers, especially the ectoderm, for further brain development. Furthermore, Bad defects involved in three-germ-layers development at 8 hpf were identified by in situ hybridization approach on cyp26, rtla, and Sox17 pattern expression markers. Finally, the Bad knockdown-induced severely defected brain was examined by tissue section from 24 to 48 h postfertilization (hpf), which correlated to induce dramatic malformation in the hindbrain. Our data suggest that the BH3-only molecule Bad regulates brain development via controlling programmed cell death on overcoming environmental stress for reducing secondary cell death signaling, which suggests that correlates to brain developmental and neurological disorders in this model system.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping