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Related Experiment Videos

Key apoptosis regulating proteins are down-regulated during postnatal tissue development.

Shane D Madden1, Maryanne Donovan, Thomas G Cotter

  • 1Cell Development and Disease Laboratory, Department of Biochemistry, Biosciences Institute, University College, Cork, Ireland.

The International Journal of Developmental Biology
|July 10, 2007
PubMed
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Key apoptotic pathway proteins like Bim, Apaf-1, and caspase-3 are down-regulated in developing murine tissues, except in the adult thymus where apoptosis persists. This suggests tissue-specific regulation of programmed cell death.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • The intrinsic apoptotic pathway is crucial for development.
  • Key mediators like Bim, Apaf-1, and caspase-3 are down-regulated in the retina post-development.
  • This down-regulation pattern is observed in other tissues.

Purpose of the Study:

  • To investigate the expression patterns of intrinsic apoptotic pathway proteins in various murine tissues during postnatal development.
  • To determine if the down-regulation of Bim, Apaf-1, and caspase-3 is a general feature of developing tissues.
  • To examine the role of apoptosis in adult thymus function.

Main Methods:

  • Western blotting or immunohistochemistry to assess protein expression levels of Bim, Apaf-1, caspase-3, and caspase-9.

Related Experiment Videos

  • TUNEL (TdT-mediated dUTP nick end labeling) assay to detect apoptotic cells.
  • Comparative analysis of protein expression and apoptosis incidence across different tissues (brain, heart, skeletal muscle, retina, cerebellum, brain stem, hippocampus, thymus) at various developmental stages.

    • Main Results:

    • Down-regulation of Bim, Apaf-1, and caspase-3 was observed in the brain, heart, and skeletal muscle during postnatal development.
    • Caspase-9 expression showed distinct patterns across different tissues.
    • Peripheral cells of the cerebellum's internal granular layer, brain stem, and hippocampus CA3 region maintained expression of these apoptotic proteins.
    • Apoptosis, detected by TUNEL assay, decreased in most developing tissues correlating with protein down-regulation.
    • The adult thymus maintained high levels of Bim, Apaf-1, and caspase-3, with persistent apoptosis.

    Conclusions:

    • Post-mitotic tissues exhibit down-regulation of key apoptotic proteins during development.
    • The thymus is an exception, requiring sustained apoptosis and expression of apoptotic proteins for function in adulthood.
    • Tissue-specific regulation of the intrinsic apoptotic pathway is critical for both development and adult tissue homeostasis.