Article first published online: 23 APR 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 55, Issue 6, pages 1985–1993, June 2012
How to Cite
Xu, L., Yin, W., Xia, J., Peng, M., Li, S., Lin, S., Pei, D. and Shu, X. (2012), An antiapoptotic role of sorting nexin 7 is required for liver development in zebrafish. Hepatology, 55: 1985–1993. doi: 10.1002/hep.25560
Potential conflict of interest: Nothing to report.
This work was supported by the “Strategic Priority Research Program” of the Chinese Academy of Sciences (XDA01020401, XDA01020307), the National Natural Science Foundation of China (30871404, 90813033), the Ministry of Science and Technology 973 Program (2009CB941102), the National Science Fund for Distinguished Young Scholars (30725012), and the CAS 100-Talent Project (to X.S.).
- Issue published online: 29 MAY 2012
- Article first published online: 23 APR 2012
- Accepted manuscript online: 27 DEC 2011 01:49AM EST
- Manuscript Accepted: 15 DEC 2011
- Manuscript Received: 11 JUL 2011
Sorting nexin (SNX) family proteins are best characterized for their abilities to regulate protein trafficking during processes such as endocytosis of membrane receptors, endosomal sorting, and protein degradation, but their in vivo functions remain largely unknown. We started to investigate the biological functions of SNXs using the zebrafish model. In this study, we demonstrated that SNX7 was essential for embryonic liver development. Hepatoblasts were specified normally, and the proliferation of these cells was not affected when SNX7 was knocked down by gene-specific morpholinos; however, they underwent massive apoptosis during the early budding stage. SNX7 mainly regulated the survival of cells in the embryonic liver and did not affect the viability of cells in other endoderm-derived organs. We further demonstrated that down-regulation of SNX7 by short interfering RNAs induced apoptosis in cell culture. At the molecular level, the cellular FLICE-like inhibitory protein (c-FLIP)/caspase 8 pathway was activated when SNX7 was down-regulated. Furthermore, overexpression of c-FLIPS was able to rescue the SNX7 knockdown-induced liver defect.
SNX7 is a liver-enriched antiapoptotic protein that is indispensable for the survival of hepatoblasts during zebrafish early embryogenesis. (HEPATOLOGY 2012;55:1985–1993)