|ZFIN ID: ZDB-PUB-060816-6|
Delineation of the cell-extrinsic apoptosis pathway in the zebrafish
Eimon, P.M., Kratz, E., Varfolomeev, E., Hymowitz, S.G., Stern, H., Zha, J., and Ashkenazi, A.
|Source:||Cell death and differentiation 13(10): 1619-1630 (Journal)|
|Registered Authors:||Kratz, Erica, Stern, Howard|
|Keywords:||Apo2L/TRAIL, death receptor, caspase, TNF superfamily, hematopoiesis|
|PubMed:||16888647 Full text @ Cell Death Differ.|
Eimon, P.M., Kratz, E., Varfolomeev, E., Hymowitz, S.G., Stern, H., Zha, J., and Ashkenazi, A. (2006) Delineation of the cell-extrinsic apoptosis pathway in the zebrafish. Cell death and differentiation. 13(10):1619-1630.
ABSTRACTThe mammalian extrinsic apoptosis pathway is triggered by Fas ligand (FasL) and Apo2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL). Ligand binding to cognate receptors activates initiator caspases directly in a death-inducing signaling complex. In Drosophila, TNF ligand binding activates initiator caspases indirectly, through JNK. We characterized the extrinsic pathway in zebrafish to determine how it operates in a nonmammalian vertebrate. We identified homologs of FasL and Apo2L/TRAIL, their receptors, and other components of the cell death machinery. Studies with three Apo2L/TRAIL homologs demonstrated that they bind the receptors zHDR (previously linked to hematopoiesis) and ovarian TNFR (zOTR). Ectopic expression of these ligands during embryogenesis induced apoptosis in erythroblasts and notochord cells. Inhibition of zHDR, zOTR, the adaptor zFADD, or caspase-8-like proteases blocked ligand-induced apoptosis, as did antiapoptotic Bcl-2 family members. Thus, the extrinsic apoptosis pathway in zebrafish closely resembles its mammalian counterpart and cooperates with the intrinsic pathway to trigger tissue-specific apoptosis during embryogenesis in response to ectopic Apo2L/TRAIL expression.