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DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3

C D'Sa-Eipper1, J R Leonard, G Putcha

  • 1Department of Pathology, Division of Neuropathology, Washington University School of Medicine, St Louis, MO 63110, USA.

Development (Cambridge, England)
|November 28, 2000
PubMed

Insights

DNA damage triggers programmed cell death (apoptosis) in neural precursor cells via p53 and caspase 9. This pathway differs from normal brain development, highlighting distinct apoptosis regulators.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cellular Biology

Background:

  • Programmed cell death (apoptosis) is crucial for brain development.
  • The roles of Bcl2 and caspase families in DNA damage-induced neuronal apoptosis are not fully understood.
  • Understanding these pathways is vital for comprehending neural precursor cell regulation.

Purpose of the Study:

  • To elucidate the molecular mechanisms of DNA damage-induced apoptosis in telencephalic neural precursor cells.
  • To investigate the involvement of p53, Bax, Bcl2 family members, and caspases in this process.
  • To compare the apoptotic pathways triggered by DNA damage versus neurotrophic factor deprivation.

Main Methods:

  • Utilized drug and gamma-irradiation to induce DNA damage in neural precursor cells from wild-type and genetically modified mice.
  • Examined apoptosis in vitro and in vivo.
  • Assessed the expression and function of key apoptosis-related genes, including p53, Bax, Bclx, Bcl2, and caspases (3 and 9).
  • Monitored cytochrome c release from mitochondria.

Main Results:

  • DNA damage-induced neural precursor cell apoptosis is dependent on p53 and caspase 9.
  • Bax and caspase 3 expression were not essential for this apoptotic pathway.
  • Disruptions in Bclx and Bcl2 did not affect DNA damage-induced apoptosis.
  • Unlike apoptosis from trophic factor withdrawal, this process did not involve detectable cytochrome c release.

Conclusions:

  • The apoptotic pathway activated by DNA damage in neural precursor cells relies on p53 and caspase 9.
  • This pathway is distinct from the one involved in normal brain morphogenesis, which requires caspase 3 and p53-independently.
  • Additional apoptotic stimuli likely regulate neural precursor cell numbers during development.

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