PUBLICATION

YAF2 inhibits caspase 8-mediated apoptosis and regulates cell survival during zebrafish embryogenesis

Authors
Stanton, S.E., McReynolds, L.J., Evans, T., and Schreiber-Agus, N.
ID
ZDB-PUB-060816-10
Date
2006
Source
The Journal of biological chemistry   281(39): 28782-28793 (Journal)
Registered Authors
Evans, Todd
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Apoptosis Regulatory Proteins/physiology*
  • Caspase 8/metabolism*
  • Cell Survival
  • DNA-Binding Proteins/physiology*
  • Gene Expression Regulation, Developmental*
  • In Situ Hybridization
  • Molecular Sequence Data
  • Phenotype
  • Phylogeny
  • Sequence Homology, Amino Acid
  • Zebrafish
  • Zebrafish Proteins/physiology*
PubMed
16891308 Full text @ J. Biol. Chem.
Abstract
Rybp (DEDAF) is a member of the Rybp/Yaf2 protein family and has been shown to encode pro-apoptotic functions and to be essential for mouse embryogenesis. The related Yaf2 protein has not been studied extensively at the cellular or organismal levels. Here we describe zebrafish yaf2 (zyaf2) and show that it is widely expressed during early embryogenesis, with subsequent enrichment of transcripts in the anterior head region. Depletion of zYaf2 during embryogenesis using specific morpholinos activates a wide-spread program of apoptosis and causes developmental arrest before the one somite stage. Partial depletion of Yaf2, achieved by injecting lower dosages of morpholino, circumvents the early arrest but leads to CNS degeneration associated with excessive apoptosis. These phenotypes can be rescued by co-injection of human YAF2 mRNA with the morpholinos or by treatment with a pan-Caspase inhibitor or a Caspase 8-specific inhibitor. Finally, the observed activation of Caspase 8 in the morphants is in accord with the ability of Yaf2 to inhibit Caspase 8-mediated apoptosis in cultured cells. Our findings implicate Yaf2 as a survival factor during early zebrafish development and organogenesis. This may suggest that Yaf2 and Rybp can encode opposing functions in the regulation of apoptosis.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping