Positional BMP signaling orchestrates villus length in the small intestine

• Published in: Nature communications Vol. 16; no. 1; pp. 5461 - 19
• Main Authors: Wang, Xu, Li, Siqi, Liu, Yuan, Kuang, Xiangyu, Chen, Jianxin, Yu, Pei, Zhao, Lianzheng, Zhang, Ze, Huang, Meimei, Liu, Liansheng, Zhang, Mengxian, Wang, Yalong, Ji, Weizhi, Li, Jinsong, Zhang, Lei, Chen, Ye-Guang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/100; 13/109; 13/51; 13/95; 14/19; 14/32; 14/35; 38/39; 38/91; 49/90; 49/91; 631/114/2391; 631/136/142; 64/60; 64/86; 82/80; Animals; Apoptosis; Bone morphogenetic proteins; Bone Morphogenetic Proteins - metabolism; Cell death; Cell Proliferation; Cell signaling; Duodenum; Duodenum - cytology; Duodenum - metabolism; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Epithelium; Humanities and Social Sciences; Ileum; Integrins - metabolism; Intestinal Mucosa - cytology; Intestinal Mucosa - metabolism; Intestine; Intestine, Small - cytology; Intestine, Small - metabolism; Jejunum; Labeling; Male; Mathematical models; Mice; Mice, Inbred C57BL; multidisciplinary; Regions; Regulatory mechanisms (biology); Science; Science (multidisciplinary); Signal Transduction; Small intestine; Stem cells; Villus; Wnt protein; Wnt Signaling Pathway
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-025-60643-2

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. BMP signaling forms an intestinal gradient regulating villus length by balancing cell proliferation with apoptosis to optimize nutrient absorption efficiency across regions.