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 and Ye-Guang Chen ()
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Xu Wang: Guangzhou National Laboratory
Siqi Li: Guangzhou National Laboratory
Yuan Liu: Tsinghua University
Xiangyu Kuang: Peking University
Jianxin Chen: University of Chinese Academy of Sciences
Pei Yu: Guangzhou National Laboratory
Lianzheng Zhao: Tsinghua University
Ze Zhang: Guangzhou National Laboratory
Meimei Huang: Guangzhou National Laboratory
Liansheng Liu: Guangzhou National Laboratory
Mengxian Zhang: Tsinghua University
Yalong Wang: Guangzhou National Laboratory
Weizhi Ji: Kunming University of Science and Technology
Jinsong Li: University of Chinese Academy of Sciences
Lei Zhang: Peking University
Ye-Guang Chen: Guangzhou National Laboratory

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60643-2

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