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Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3
08:20

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3

Published on: December 20, 2013

Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development

W C Yeh1, A Itie, A J Elia

  • 1Amgen Institute, Department of Medical Biophysics, University of Toronto and Ontario Cancer Institute, Canada.

Immunity
|July 14, 2000
PubMed

Insights

Casper (c-FLIP) protein is crucial for embryonic development and heart formation. Casper deficiency leads to embryonic lethality and increased sensitivity to cell death, highlighting its dual role in development and cytoprotection.

Area of Science:

  • Cellular and Molecular Biology
  • Developmental Biology
  • Immunology

Background:

  • Casper (c-FLIP) is a known inhibitor of apoptosis that interacts with FADD and caspase-8 in death receptor signaling pathways.
  • Deficiency in FADD or caspase-8 leads to embryonic lethality, suggesting their critical roles in development.

Purpose of the Study:

  • To investigate the physiological functions of Casper (c-FLIP) by generating and analyzing Casper-deficient mice and cells.
  • To elucidate the distinct roles of Casper in embryonic development and cellular apoptosis regulation.

Main Methods:

  • Generation of Casper-deficient (casper-/-) mice and embryonic fibroblasts.
  • Phenotypic analysis of casper-/- embryos, focusing on survival and heart development.
  • Assessment of apoptosis sensitivity in casper-/- cells upon stimulation with FasL or TNF.
  • Analysis of NF-kappaB and JNK/SAPK activation in TNF-stimulated casper-/- cells.

Main Results:

  • Casper-deficient embryos exhibit embryonic lethality around day 10.5 with impaired heart development, similar to FADD-/- and caspase-8-/- embryos.
  • Casper-deficient embryonic fibroblasts are hypersensitive to FasL- and TNF-induced apoptosis, with rapid caspase activation.
  • NF-kappaB and JNK/SAPK activation remain intact in TNF-stimulated casper-/- cells, despite increased apoptosis.

Conclusions:

  • Casper (c-FLIP) plays a dual role: essential for embryonic development, likely in cooperation with FADD and caspase-8.
  • Casper also functions as a cytoprotective factor, inhibiting death receptor-mediated apoptosis.

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