Mechanisms Of Zebrafish Liver Development:a Role Of Sorting Nexin7

Liver is the largest and also the most important metabolism‐related internal organ in vertebrate, liver correlative diseases always a substantial threaten of health. To elucidate the liver’s developmental process and how does this organ exercise its physiological fuction, always been a important and intriguing research area of biological and medical science. Sorting Nexin（SNX） is a gene family which shares the Phox（PX） domain, most SNX genes locate on the endomembrane system and play important role in the transport and sorting process of proteins. There are33SNXs which have been discovered and named in human genome, but we still know very little about the physiologic fuction of this conservative and apparently important family. In this paper, we use a model organism:Zebrafish, to study the potential fuction of SNXs from individual and organ level, throμgh our research, we discovered SNX7specifically expressed in the liver cell, low‐expressing level of SNX7causes severe repress liver development and almost with no influence to other internal organ. Further research revealed that knockdown of SNX7by morpholino‐microinjection does’t affect the process that original precursor cells differentiate into hepatoblast, but SNX7do severely inhibit the following growing/proliferating/maturing procedure. At the molecular level, we found that several pro‐apoptotic molecules including Caspase8, bax, p53and its target genes were up‐regulated in SNX7morphants. We concluded that an anti‐apoptotic signaling pathway involving SNX7was indispensible for the survival of hepatoblasts during embryonic liver development. In the in Vitro part,we induced apoptosis in HeLa celline by transfection of SNX7siRNAs,finally,we found the crucial molecular connect SNX7and apoptosis was c‐FLIPS,we then proved it by rescue test.In this research,we combine multiple research methods, both in vivo and in vitro, to explore how SNX7regulate the development of endodermal organs, especially how SNX7regulates the growing/proliferating/maturing process of hepatoblast, we want to find the upstream and downstream signaling pathways of SNX7‐regulating‐liver‐development, our goal is build a network of signaling pathways of SNX7regulating process, to elucidate the mechanism of such process from different researching leve:molecular,cellular,organic and even embryoic and individual.