Smad7的高表达与肠道肿瘤的发生、发展和预后相关。申请人参与了Rosa-Smad7条件性基因敲入(CKI)小鼠的构建，用Cre-LoxP系统在小鼠肠道上皮或间质稳定表达Smad7，该CKI小鼠或在胚胎时期死亡，或在出生后存活，但自发产生不同类型的肠道肿瘤，提示Smad7影响胚胎期和出生后肠道细胞的发育及功能维持。为进一步阐明Smad7在不同鼠龄肠道发育及肿瘤形成中的作用机理，本课题在肠上皮、隐窝成体干细胞及间质分时段选择性上调Smad7，检测该基因对胎鼠、幼鼠及成年鼠肠道发育的影响。结合体外细胞过表达/剔降实验，用RNA-Seq、IHC/IF、qPCR、Western Blottting等方法鉴定Smad7影响肠上皮细胞、间质细胞、肌细胞发育与分化的效应分子，进一步证实Smad7在肠道形成和生理稳态，特别是上皮与间质交互作用中的功能，有望明确Smad7在肠道发育及肿瘤形成中的分子机制。

High expression of Smad7 is associated with tumorigenesis, progression, and prognosis of intestinal tumor. We participated in the engineering of Rosa-Smad7 conditional knock-in (CKI) mice. By cross-breeding these mice to the mice with specific expression of Cre in intestinal epithelia and mesenchyme respectively using Cre-LoxP system, we found some of offspring may die in embryonic period while others survived postnatally, but show enhanced intestinal tumorogenesis, suggesting that Smad7 affects the intestinal development and homeostasis. To explore the role of Smad7 in intestinal development and tumorigenesis in different growing ages, this project proposes to up-regulate Smad7 expression in intestinal epithelial, crypt stem cell and/or mesenchymal at different development stage selectively, then characters the malformation and tumorigenesis of intestine. We will also up/down regulate the effector molecules of Smad7 in epithelia, mesenchyme and muscle cells, to further confirm the role of Smad7 played in intestine development and function maintaining especially the interaction between epithelia and mesenchyme, using RNA-Seq, IHE/IF, qPCR, Western Blotting and other techniques. The proposed studies will help unlock the molecular mechanism of Smad7 in the intestinal development and tumorigenesis.