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Developmental cell death during Xenopus metamorphosis involves BID cleavage and caspase 2 and 8 activation

D Du Pasquier1, V Rincheval, L Sinzelle

  • 1Laboratoire de Transgenèse et Génétique des Amphibiens, CNRS UMR 8080, IBAIC, Université Paris-Sud, Orsay Cedex, France.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|June 21, 2006
PubMed

Insights

During Xenopus metamorphosis, the BID protein and Caspases-2 and -8 initiate apoptosis, leading to tadpole organ regression. This study reveals a key step in the programmed cell death pathway during amphibian development.

Area of Science:

  • Developmental Biology
  • Cell Death Research
  • Molecular Biology

Background:

  • Tadpole organ loss during metamorphosis primarily occurs via apoptosis.
  • The mitochondrial death pathway, involving Bax, caspase-3, and caspase-9, is implicated.
  • Upstream regulators of Bax activation in this process remain largely unknown.

Purpose of the Study:

  • To investigate the role of BH3-only proteins, specifically BID, in the upstream regulation of apoptosis during Xenopus metamorphosis.
  • To elucidate the involvement of caspases-2 and -8 in tail regression.
  • To understand the hormonal regulation and organ autonomy of this apoptotic pathway.

Main Methods:

  • Quantitative analysis of Xenopus bid transcript levels during metamorphosis.
  • Monitoring of Caspase-2 and -8 mRNA levels and activity.
  • Utilizing BIDGFP transgenic Xenopus tadpoles to observe tail regression dynamics.
  • Employing caspase-8 inhibitors to assess their impact on BIDGFP cleavage and metamorphosis.

Main Results:

  • Xenopus bid transcript levels and Caspase-2 and -8 mRNA levels/activity increase during metamorphosis in regressing larval cells.
  • Accelerated tail regression observed in BIDGFP transgenic tadpoles.
  • Caspase-8 inhibitors blocked BIDGFP cleavage during natural and T(3)-induced metamorphosis.

Conclusions:

  • The thyroid hormone (T(3)) induces an organ-autonomous apoptotic pathway during Xenopus metamorphosis.
  • This pathway involves the cell death executioners BID, Caspase-2, and Caspase-8.
  • BID acts upstream in initiating the caspase cascade leading to tadpole organ regression.

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