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Related Experiment Videos

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.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|July 29, 2005
PubMed
Summary

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.

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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.

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  • 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.