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In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Bcl-X(L)-caspase-9 interactions in the developing nervous system: evidence for multiple death pathways
A U Zaidi1, C D'Sa-Eipper, J Brenner
1Department of Pathology and Immunology, Division of Neuropathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Summary
Bcl-X(L) and Caspase-9 have both independent and overlapping roles in programmed cell death during nervous system development. Their interaction influences neuronal apoptosis pathways, shifting from Caspase-9 to Bax and Bcl-X(L) mediation.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Programmed cell death is essential for nervous system development, regulated by Bcl-2 and Caspase families.
- Bcl-X(L) deficiency causes excessive immature neuron death; Caspase-9 deficiency leads to reduced apoptosis and developmental issues.
Purpose of the Study:
- To investigate the interaction between Bcl-X(L) and Caspase-9 in neuronal apoptosis.
- To elucidate the roles of Bcl-2 and Caspase family members in telencephalic neuron apoptosis induced by cytosine arabinoside (AraC).
Main Methods:
- Generation of bcl-x/caspase-9 double homozygous mutant mice.
- In vitro analysis of AraC-induced apoptosis in telencephalic neurons from various gene-deficient mice (Bcl-X(L), Bax, Caspase-9, Caspase-3, p53).
Main Results:
- Caspase-9 deficiency completely rescued the increased neuronal apoptosis in Bcl-X(L)-deficient embryos.
- Double mutants (bcl-x(-/-)/caspase-9(-/-)) showed neurodevelopmental abnormalities similar to Caspase-9 single mutants.
- p53- and Bax-deficient neurons were protected from AraC-induced apoptosis, unlike Caspase-9 and Caspase-3 deficient neurons.
Conclusions:
- Bcl-X(L) and Caspase-9 exhibit both epistatic and independent functions in neuronal programmed cell death.
- Apoptotic pathways in telencephalic neurons transition from Caspase-9-mediated to Bax- and Bcl-X(L)-mediated processes.
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