Xu, L., Yin, W., Xia, J., Peng, M., Li, S., Lin, S., Pei, A., and Shum, X. (2012) An anti-apoptotic role of SNX7 is required for liver development in zebrafish. Hepatology (Baltimore, Md.). 55(6):1985-1993.
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 it did not affect the viability of cells in other endoderm derived organs. We further demonstrated that down-regulation of SNX7 by siRNAs induced apoptosis in cell culture. At the molecular level, the c-FLIP/caspase 8 pathway was activated when SNX7 was down-regulated. Furthermore, over-expression of c-FLIPs was able to rescue the SNX7 knockdown induced liver defect. Conclusion: SNX7 is a liver-enriched anti-apoptotic protein which is indispensable for the survival of hepatoblasts during zebrafish early embryogenesis.