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Published on: February 13, 2014
Widespread elimination of naturally occurring neuronal death in Bax-deficient mice
F A White1, C R Keller-Peck, C M Knudson
1Department of Neurology, Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Abstract:
The proapoptotic molecule BAX is required for death of sympathetic and motor neurons in the setting of trophic factor deprivation. Furthermore, adult Bax-/- mice have more motor neurons than do their wild-type counterparts. These findings raise the possibility that BAX regulates naturally occurring cell death during development in many neuronal populations. To test this idea, we assessed apoptosis using TUNEL labeling in several well-studied neural systems during embryonic and early postnatal development in Bax-/- mice. Remarkably, naturally occurring cell death is virtually eliminated between embryonic day 11.5 (E11.5) and postnatal day 1 (PN1) in most peripheral ganglia, in motor pools in the spinal cord, and in the trigeminal brainstem nuclear complex. Additionally, reduction, although not elimination, of cell death was noted throughout the developing cerebellum, in some layers of the retina, and in the hippocampus. Saving of cells was verified by axon counts of dorsal and ventral roots, as well as facial and optic nerves that revealed 24-35% increases in axon number. Interestingly, many of the supernumerary axons had very small cross-sectional areas, suggesting that the associated neurons are not normal. We conclude that BAX is a critical mediator of naturally occurring death of peripheral and CNS neurons during embryonic life. However, rescue from naturally occurring cell death does not imply that the neurons will develop normal functional capabilities.
Insights
The proapoptotic molecule BAX is essential for neuronal death during development. Eliminating BAX nearly stops naturally occurring cell death in many developing neurons, suggesting BAX
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Death Research
Background:
- The proapoptotic molecule BAX plays a role in neuronal death when deprived of trophic factors.
- Bax-/- mice exhibit increased motor neuron counts in adulthood.
- These observations suggest BAX involvement in developmental neuronal cell death.
Purpose of the Study:
- To investigate the role of BAX in naturally occurring neuronal cell death during embryonic and early postnatal development.
- To determine if BAX regulates apoptosis in various neuronal populations.
- To assess the impact of BAX deficiency on neuronal survival and development.
Main Methods:
- Utilized TUNEL labeling to assess apoptosis in Bax-/- mice across different developmental stages.
- Examined neuronal populations in the peripheral nervous system, spinal cord, brainstem, cerebellum, retina, and hippocampus.
- Quantified axon numbers in cranial and spinal nerves to verify cell survival.
Main Results:
- Naturally occurring cell death was significantly reduced, almost eliminated, in most peripheral ganglia, spinal cord motor pools, and the trigeminal brainstem nuclei between E11.5 and PN1.
- A reduction in cell death was also observed in the developing cerebellum, retina, and hippocampus.
- Axon counts revealed a 24-35% increase in dorsal/ventral roots and facial/optic nerves, though many supernumerary axons were small, indicating potential abnormalities.
Conclusions:
- BAX is a critical mediator of naturally occurring cell death in both peripheral and central nervous system neurons during embryonic development.
- While BAX deficiency rescues neurons from programmed cell death, it does not guarantee normal functional development.
- Further research is needed to understand the long-term implications of BAX-mediated cell death regulation on neuronal function.
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