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Updated: Aug 16, 2026
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Essential role for survivin in early brain development
Yuying Jiang1, Alain de Bruin, Hugo Caldas
1Center for Childhood Cancer, Columbus Children's Research Institute, Columbus, Ohio 43205, USA.
Abstract:
Apoptosis is an essential process during normal neuronal development. Approximately one-half of the neurons produced during neurogenesis die before completion of CNS maturation. To characterize the role of the inhibitor of apoptosis gene, survivin, during neurogenesis, we used the Cre-loxP-system to generate mice lacking survivin in neuronal precursor cells. Conditional deletion of survivin starting at embryonic day 10.5 leads to massive apoptosis of neuronal precursor cells in the CNS. Conditional mutants were born at the expected Mendelian ratios; however, these died shortly after birth from respiratory insufficiency, without primary cardiopulmonary pathology. Newborn conditional mutants showed a marked reduction in the size of the brain associated with severe, mutifocal apoptosis in the cerebrum, cerebellum, brainstem, spinal cord, and retina. Caspase-3 and caspase-9 activities in the mutant brains were significantly elevated, whereas bax expression was unchanged from controls. These results show that survivin is critically required for the survival of developing CNS neurons, and may impact on our understanding of neural repair, neural development, and neurodegenerative diseases. Our study is the first to solidify a role for survivin as an antiapoptotic protein during normal neuronal development in vivo.
Insights
Survivin is crucial for preventing excessive neuronal cell death during brain development. Deleting survivin in developing neurons causes widespread apoptosis and lethality in newborn mice.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Apoptosis, or programmed cell death, is vital for normal neuronal development.
- Significant neuron loss occurs during central nervous system (CNS) maturation.
- The role of survivin, an inhibitor of apoptosis protein, in neurogenesis requires further elucidation.
Purpose of the Study:
- To investigate the function of survivin in neuronal precursor cells during embryonic development.
- To determine the consequences of survivin deficiency on neurogenesis and CNS formation in vivo.
Main Methods:
- Utilized the Cre-loxP system to generate conditional knockout mice with survivin deleted in neuronal precursor cells.
- Analyzed developmental apoptosis, survival rates, and CNS morphology in mutant mice.
- Assessed caspase and bax expression levels in the brains of conditional mutants.
Main Results:
- Conditional deletion of survivin from embryonic day 10.5 resulted in massive apoptosis of CNS neuronal precursor cells.
- Mutant mice exhibited reduced brain size and multifocal apoptosis across the CNS and retina.
- Elevated caspase-3 and caspase-9 activities were observed, while bax expression remained unchanged.
Conclusions:
- Survivin is essential for the survival of developing CNS neurons.
- This finding has implications for understanding neural repair, development, and neurodegenerative diseases.
- The study establishes survivin's critical antiapoptotic role in vivo during normal neuronal development.
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