Abstract
Although the role of the b-cell lymphoma (Bcl)-2 family of apoptosis inhibitors is well documented in tumor cells and tissue morphogenesis, their role during the early development of vertebrates is unknown. Here, we characterize Nrz, a new Bcl-2-related inhibitor of apoptosis in zebrafish. Nrz is a mitochondrial protein, antagonizing the death-accelerator Bax. The nrz gene is mainly expressed during gastrulation and somitogenesis. The knockdown of nrz with antisense morpholinos leads to alterations of the somites, correlated with an increase in apoptosis. In addition, earlier during development, in the zebrafish gastrula, nrz knockdown results in an increase of snail-1 expression at the margin and frequent gastrulation arrest at the shield stage, independently of apoptosis. Together these data suggest that Nrz, in addition to its effect on apoptosis, contributes to cell movements during gastrulation by negatively regulating the expression of Snail-1, a transcription factor that controls cell adhesion.
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Abbreviations
- BCL:
-
b-cell lymphoma
- BH-3:
-
bcl-2 homology domain 3
- DMEM:
-
Dulbecco's minimal essential medium
- EMT:
-
epithelial mesenchymal transition
- E-YSL:
-
external yolk syncitial layer
- FITC:
-
fluoresceine isothiocyanate
- HPF:
-
hours post fertilization
- HVT:
-
herpes virus of turkeys
- I-YSL:
-
internal yolk syncitial layer
- MO:
-
morpholino
- NR-13:
-
neuroretina clone 13
- ORF:
-
open reading frame
- PBS:
-
phosphate buffer saline
- PCD:
-
programmed cell death
- RT-PCR:
-
reverse transcriptase-polymerase chain reaction
- TGF:
-
transforming growth factor
- TM:
-
transmembrane domain
- YSL:
-
yolk syncitial layer
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Acknowledgements
Many thanks to L Bernard for organizing the zebrafish facilities. We thank J Gouttenoire, F Mallein-Gerin and P Blader for help and comments. B Thisse and A Yamamoto are acknowledged for zebrafish probes. This work was supported by Retina France, the ARC, the région Rhône-Alpes and the CNRS. EA was supported by the Ligue nationale contre le cancer (comité de Haute Savoie). AA was supported by the CNRS and the FRM. KFF was supported by the région Rhône-Alpes and EMBO.
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Arnaud, E., Ferri, K., Thibaut, J. et al. The zebrafish bcl-2 homologue Nrz controls development during somitogenesis and gastrulation via apoptosis-dependent and -independent mechanisms. Cell Death Differ 13, 1128–1137 (2006). https://doi.org/10.1038/sj.cdd.4401797
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DOI: https://doi.org/10.1038/sj.cdd.4401797
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