2. Academic Validation
  3. Mesenchymal SLMAP coordinates with MST3 to govern gut elongation during development

Mesenchymal SLMAP coordinates with MST3 to govern gut elongation during development

  • Development. 2025 Oct 15;152(20):dev204483. doi: 10.1242/dev.204483.
Yuwei Pan 1,  Shiyang Wang 1,  Wuqi Yang 2,  Xi Wu 1,  Hanfu Zhang 1,  Sujuan Du 3 4,  Mingxin Zhang 1,  Liyuan Hou 2,  Maksim V Plikus 5,  Jianwei Shuai 6 7,  Cong Lv 2,  Lu Yu 1,  Zhengquan Yu 1 3 4 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
  • 2 Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
  • 3 State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, The First Affiliated Hospital of Zhengzhou University, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, China.
  • 4 Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, China.
  • 5 Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
  • 6 Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China.
  • 7 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China.
  • 8 State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450052, China.
PMID: 40521668 DOI: 10.1242/dev.204483
Abstract

Developing gut in mice undergoes rapid elongation during late embryogenesis, yet significantly slows down after birth. The precise regulatory mechanism of this dynamic morphogenetic process remains unknown. By utilizing single-cell RNA-sequencing analysis, we show that YAP activity in intestinal fibroblasts is the major molecular contributor to gut elongation. To determine how mesenchymal YAP activity is controlled, we identified canonical sarcolemma membrane-associated protein (SLMAP) as its critical regulator during mouse embryonic gut morphogenesis. Deleting Slmap in gut mesenchyme impairs YAP activity, leading to a short gut and a significant decrease in intestinal epithelial cell proliferation. Mechanistically, SLMAP activates YAP by directly regulating MST3 kinase. Physiologically, MST3 levels prominently increase over the developmental time, reaching their peak on postnatal day (P)14, when gut elongation in mice slows down. Depleting Mst3 in mesenchyme results in increased gut length at P14 accompanied by enhanced YAP activity. Importantly, a short gut phenotype in mesenchyme-specific Slmap mutant mice is partially compensated for by concomitant deletion of mesenchymal Mst3. Taken together, our findings demonstrate that SLMAP interacts with MST3 kinase to regulate the mesenchymal YAP activity that governs dynamic gut elongation across embryonic and postnatal development.

Keywords

Gut elongation; Mesenchyme; Mst3; Slmap; Yap.

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