胎盘皱褶的形成是猪胎盘发育的重要特征，对胎儿发育与存活起关键作用，胎盘绒毛膜上皮细胞形状由柱状向立方状转换是皱褶形成的结构基础。申请人前期研究发现妊娠后期的绒毛膜上皮细胞形状在大白猪胎盘皱褶顶端为柱状、底侧部为立方状，而在梅山猪中则全部为立方状，胞间连接蛋白如E-cadherin等只在柱状绒毛膜上皮细胞中高表达，而其负调控转录因子ZEB2却只在立方状细胞中高表达，表明ZEB2可能靶向胞间连接基因，调控绒毛膜上皮细胞形状的改变。本项目拟以梅山和大白猪妊娠后期的胎盘绒毛膜为材料，采用荧光激活细胞分选技术获得两种形状的绒毛膜上皮细胞，结合RNA-Seq和ChIP-Seq及EMSA等技术分析ZEB2的靶基因及上游调控因子，在猪细胞和组织学水平及条件性基因敲除动物模型中鉴定ZEB2介导的调控猪胎盘褶皱绒毛膜上皮细胞形状转换的信号通路，为解析猪胎盘发育的机制奠定基础，为母猪繁殖效率的遗传改良提供依据。

The development of the placental folded structure is of importance in pigs to expand the maternal-fetal exchange surface area and then to maintain the pregnancy and fetal survival.The shape of chorionic epithelial cell changes during the development of placenta and have the impact on the formation of the placental folded structure.Our previous work found that in Large White pigs of day 95 gestation , the shape of chorionic epithelial cells at the top of the folded placenta was columnar but was cuboidal at the bottom of the folded placenta. However, in Meishan pig, all of the chorionic epithelial cells showed cuboidal shape.The proteins for cell adhesion such as E-cadherin were highly expressed in columnar chorionic epithelial cells, while the E-cadherin transcriptional repressor of ZEB2 was found to be highly expressed in cuboidal chorionic epithelial cells, indicating that ZEB2 may induce cell shape change by regulation of the expression of the proteins for cell adhesion. Therefore, the study will investigate the signaling pathway mediated by ZEB2 in regulation of chorionic epithelial cell shape change by using the ChIP-Seq, RNA-Seq and EMSA approaches .Characterization of the mechanism involved will carried out in the cell culture model, the pig placental tissue, and conditional gene knockout animal model. Knowledge gained will be of significance for the characterization of the mechanism regulation of the placental development and for the improvement of sow reproductive efficiency.