尿道下裂是最常见的先天性泌尿生殖畸形，严重影响患儿泌尿生殖功能。阴茎及尿道的发育高度依赖雄激素信号调控，前期研究发现，作为雄激素信号通路关键调控因子的MafB基因与尿道下裂发生密切相关，但MafB的下游信号通路及其对胚胎尿道细胞生物学的调控机制尚不清楚。本项目拟在前期系列研究基础上，从解剖学、病理学、分子生物学等多层面，围绕“尿道板上皮细胞MafB基因缺失—间质细胞增殖—上皮细胞凋亡与上皮-间质转化（EMT）异常—尿道结构畸形”的科学思路，以MafB为研究重点，从上皮-间质相互作用（EMI）角度，通过体内外实验探索MafB异常与尿道板上皮及间质细胞生物学特征改变相关性，以期揭示以MafB为中心的信号通路及尿道发育调控机制。其结果必将为阐明雄激素信号转导及尿道下裂发生机制提供重要理论与实验依据。

Hypospadias is the most common congenital genitourinary malformation, which has a profound impact on the function of children’s genitourinary system. The development of penis and urethra is highly dependent on the regulation of androgen. Previous studies have found that MafB is closely related to hypospadias as one important regulator of the androgen signaling pathway, but the downstream signaling pathway of MafB and its function on the embryonic biology of urethra still remains unknown. Based on our previous studies, we will focus on MafB and epithelial-mesenchymal interaction (EMI) from the perspectives of anatomy, pathology, and molecular biology with the idea of “MafB deletion in epithelium of urethral plat – proliferation of mesenchymal cell – apoptosis of epithelium and abnormal epithelial-mesenchymal transition (EMT) – urethral structural malformation”. To verify the signaling pathway of urethral development, we will explore the relationship between MafB and biological characteristics of epithelium and mesenchymal cells in vivo and in vitro. This study will provide a theoretical and experimental basis for the mechanism of hypospadias and androgen signaling pathway.