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Use of LysoTracker to Detect Programmed Cell Death in Embryos and Differentiating Embryonic Stem Cells
Published on: October 11, 2012
Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development
F Cecconi1, G Alvarez-Bolado, B I Meyer
1Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Göttingen, Germany.
Cell
|September 30, 1998
Summary
Apoptotic protease activating factor 1 (Apaf1) is crucial for mammalian development. Its absence leads to embryonic lethality and severe developmental defects due to impaired programmed cell death.
Area of Science:
- Developmental Biology
- Cellular Biology
- Genetics
Background:
- Apoptotic protease activating factor 1 (Apaf1) is a key component of the intrinsic apoptotic pathway.
- It mediates the activation of Caspase 9 (CASP9) and subsequently Caspase 3 (CASP3).
- The role of Apaf1 in mammalian embryonic development and programmed cell death is not fully understood.
Purpose of the Study:
- To investigate the function of Apaf1 in mammalian embryonic development.
- To determine the role of Apaf1 in programmed cell death during embryogenesis.
Main Methods:
- Generation of a gene trap null allele for murine Apaf1.
- Phenotypic analysis of homozygous Apaf1 mutant embryos.
- In situ immunodetection of Caspase 3 activation.
Main Results:
- Homozygous Apaf1 mutants exhibit embryonic lethality at day 16.5.
- Mutants display severe craniofacial malformations, brain overgrowth, persistent interdigital webs, and ocular abnormalities.
- Apaf1 deficiency results in reduced apoptotic response in fibroblasts and prevents in vivo Caspase 3 activation.
Conclusions:
- Apaf1 is essential for Caspase 3 activation in the embryonic brain.
- Apaf1 plays a critical role in regulating developmental programmed cell death in mammals.
- The absence of Apaf1 leads to severe developmental defects and embryonic lethality.
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