Positional BMP signaling orchestrates villus length in the small intestine
Xu Wang, Siqi Li, Yuan Liu, Xiangyu Kuang, Jianxin Chen, Pei Yu, Lianzheng Zhao, Ze Zhang, Meimei Huang, Liansheng Liu, Mengxian Zhang, Yalong Wang, Weizhi Ji, Jinsong Li, Lei Zhang, Ye‐Guang Chen
Abstract
The intestinal epithelium undergoes fast turnover, and the villus length in the small intestine gradually decreases from the duodenum to the ileum. However, the underlying mechanisms remain poorly understood. In this study, we investigate the regulatory mechanism underlying the regional disparity of villus length. A progressive strengthening of BMP signaling from the duodenum to the jejunum and ileum establishes a signaling gradient, resulting in differences in the rates of cell proliferation and apoptosis. We show that BMP signaling regulates the survival of the small intestine epithelial cells by inhibiting integrin expression and thereby inducing cell apoptosis. Combined with mathematical modeling, our data reveal that BMP signaling provides positional cues and antagonizes Wnt signaling to control villus growth, while Wnt signaling promotes BMP signaling to counteract excessive proliferation, thus maintaining villus length. Our findings provide insights into the signaling dynamics governing epithelial turnover and villus length in the small intestine.