Developmental cell death during Xenopus metamorphosis involves BID cleavage and caspase 2 and 8 activation.
Elimination of tadpole organs during Xenopus metamorphosis is largely achieved through apoptosis, and recent evidence suggest involvement of the mitochondrial death route and bax-initiated caspase-3 and -9 deployment. However, events upstream of the activation of Bax are unknown. In other models, proteins of the BH3-only group such as BID are known to assure this function. We show that Xenopus bid transcript levels increase at metamorphosis in larval cells destined to disappear. This increase correlates with an abrupt rise in Caspase-2 and -8 mRNA levels and an enhanced activity of Caspase-2 and -8. In BIDGFP transgenic animal's tail regression is accelerated. The cleavage of BIDGFP fusion protein during natural or T(3)-induced metamorphosis was specifically inhibited by caspase-8 inhibitors. Our results show that tail regression at metamorphosis implicates an apoptotic pathway inducible by T(3) hormone in an organ autonomous manner and involving the cell death executioners BID and Caspases-2 and -8.
Du Pasquier
D
D
Laboratoire de Transgenèse et Génétique des Amphibiens, CNRS UMR 8080, IBAIC, Université Paris-Sud, Orsay Cedex, France.
Rincheval
V
V
Sinzelle
L
L
Chesneau
A
A
Ballagny
C
C
Sachs
L M
LM
Demeneix
B
B
Mazabraud
A
A
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D053143:Caspase 2; D053181:Caspase 8; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter / Q000235:genetics; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008675:Metamorphosis, Biological; D008928:Mitochondria / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013623:Tail / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011956:Receptors, Cell Surface; D051020:bcl-X Protein; D053143:Caspase 2; D053181:Caspase 8; D020169:Caspases