分子伴侣是广泛存在于生物体内对蛋白质折叠、组装及降解起调控作用的重要分子，介导了生长发育、衰老等生理病理过程。前折叠素（PFD）作为一种分子伴侣是否调控脊椎动物生理功能目前尚不清楚，研究其早期生长发育中的功能至关重要。我们的前期研究发现模式动物斑马鱼PFD3过量表达导致了严重的发育缺陷，而且这种缺陷是通过影响早期发育的重要信号通路-经典Wnt信号通路实现的，提示PFD3可能作为重要的胚胎发育调控分子，参与了脊椎动物的早期发育。本项目拟以斑马鱼为模式动物，利用其胚胎透明、体外发育的特点，通过体内过表达、敲降和营救、cas9基因突变等方法，结合体外实验，探讨PFD3体内功能并从分子水平上分析其与Wnt/β-catenin信号通路的关键交联分子及作用机制，分析PFD功能的保守性。研究结果将全面揭示PFD3在动物早期胚胎发育中的地位作用，最终为斑马鱼作为研究前折叠素家族功能的模式生物提供依据。

Molecular chaperones are abundant, well-conserved proteins and play very important role in promoting efficient folding and preventing aggregation of proteins. The Dysfunction of molecular chaperones is associated with many pathphysiological processes such as abnormal fertilization, developmental defect, and aging. However, it is not clear that the functions of prefoldin, a chaperone, in early embyonic vertebrate development. Recently our research showed that overexpression of PFD3 in zebrafish embryo resulted in severe developmental defect and inhibited Wnt/β-catenin signaling pathway. These results indicated that PFD3 may play a vital role in early embryonic development via interaction with Wnt/β-catenin signaling pathway. In this proposal, we use zebrafish, an excellent model system in develoment research because of transparent embryos and in vitro development, to explore the role of PFD3. Combining gene overexpression, loss of function and gain of function, Cas9 gene editing with cell cuture in vitro, we will investigate the function of PFD3 in early development and how it interact with Wnt/β-catenin pathway. This study will uncover the mechanism how Wnt/β-catenin is regulated in vivo by PFD3, and ultimately provide the data for the zebrafish as a model organism in investing the functions of PFD family.