细胞稳态失衡会引起器官功能改变。申请人前期研究发现锌指蛋白Zc3h8对斑马鱼消化器官功能建成后的细胞稳态维持起重要作用，但具体机制不清楚。当其蛋白功能结构域发生突变后，会引起NF-κB信号/炎症因子等在内的多基因在消化器官中的异常表达，并引发相应的退行化表型。我们提出科学假说：在消化器官的正常功能维持过程中，存在一些既受Zc3h8直接调控又能特异性地影响NF-κB信号的活化的关键的中间因子。本项目拟通过组学分析结合基因原位表达、基因功能敲除、转基因过表达、细胞活体追踪以及分子相互作用等技术与方法：1）筛选受Zc3h8直接调控，并能特异性影响消化器官稳态维持的关键因子；2）明确其与Zc3h8和NF-κB信号通路之间的相互作用方式；3）阐明Zc3h8蛋白分子维持消化器官细胞稳态的分子机制。本研究将帮助加深理解锌指蛋白分子在维持消化器官稳态方面所起的作用。

Homeostatic imbalance may cause changes in organ function. Zinc finger protein Zc3h8 has been found in the applicant’s previous research to play a big role in maintaining the homeostasis after the function of zebrafish digestive organs was developed, but the specific mechanism is still unclear. When the protein functional domain is mutated, the abnormal expression of multiple genes including NF-κB signaling / inflammatory factors in the digestive organs will be caused, as well as the corresponding degenerative phenotype. It is proposed scientifically that certain key intermediate factors that are directly regulated by Zc3h8 and can specifically affect the activation of NF-κB signaling are available when the normal function of digestive organs is maintained. Combining genes expressions in situ, gene function knockout, transgene overexpression, cell tracking and molecular interaction, in this program, through omics analysis, it is intended to: 1) Screen the key factors that are directly regulated by Zc3h8 and can specifically affect the homeostasis maintenance of digestive organs; 2) Clarify their interaction with Zc3h8 and NF-κB signaling pathway; 3) Clarify the molecular mechanism of Zc3h8 protein molecule to maintain the homeostasis of digestive organ cells. This study will facilitate the understanding of the role of zinc finger protein molecules in maintaining the homeostasis of digestive organs.