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Published on: November 27, 2016
Roles of caspases in the programmed cell death of motoneurons in vivo
1Department of Anatomy, School of Medicine, Fukushima Medical University, Japan. h-yaginm@fmu.ac.jp
Abstract:
Cysteine proteases comprising the caspase family have been considered one of the major executioners of programmed cell death. However, detailed analyses of the programmed cell death of developing motoneurons in mice following the genetic deletion of two key caspases, casp-3 and casp-9, and in the chick embryo following treatment with caspase inhibitors, indicate that normal amounts of cell loss occur although the death process is delayed. Motoneurons undergoing programmed cell death without caspase activities exhibit a nonapoptotic morphology in which nuclear changes such as chromatin condensation are absent or reduced and which exhibit extensive cytoplasmic vacuolization such as is rarely observed in degenerating control neurons. These results suggest that caspases are involved in, but are not indispensable for, the developmental death of motoneurons, and that one function of caspases may be to facilitate the removal of cells that are destined to die. Possible alternative caspase-independent pathways for the programmed death of motoneurons are discussed.
Insights
Caspases (casp-3 and casp-9) are not essential for motoneuron programmed cell death but delay the process. Without caspases, motoneurons exhibit delayed, non-apoptotic death with distinct morphological changes.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Caspases are key executioners of programmed cell death.
- Their role in developmental motoneuron death was previously assumed essential.
Purpose of the Study:
- To investigate the necessity of caspases in developmental motoneuron programmed cell death.
- To characterize the morphology of caspase-independent cell death.
Main Methods:
- Genetic deletion of casp-3 and casp-9 in developing mouse motoneurons.
- Inhibition of caspases in chick embryo motoneurons.
- Morphological analysis of dying motoneurons.
Main Results:
- Motoneuron cell loss occurred at normal levels despite caspase absence, but was delayed.
- Caspase-deficient motoneurons showed non-apoptotic morphology with reduced chromatin condensation and cytoplasmic vacuolization.
- These findings suggest caspases facilitate, but are not indispensable for, motoneuron death.
Conclusions:
- Caspases play a role in, but are not required for, developmental motoneuron programmed cell death.
- Alternative caspase-independent pathways likely exist for motoneuron elimination.
- Caspases may function to expedite the removal of cells destined for death.
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