ArticleDevelopmental biology2011
Hedgehog signaling controls homeostasis of adult intestinal smooth muscle.
Article in Developmental biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- Enteroendocrine cell differentiation: Implications for human disease.Molecular and cellular endocrinology · 2025Review
- Gene proteins, growth factors/their receptors in the wall of chronic calculous cholecystitis-affected gallbladder children.BMC pediatrics · 2025Article
- Villus myofibroblasts are developmental and adult progenitors of mammalian gut lymphatic musculature.Developmental cell · 2024Article
- Dynamic Hippo pathway activity underlies mesenchymal differentiation during lung alveolar morphogenesis.Development (Cambridge, England) · 2024Article
- Hedgehog signaling is required for endometrial remodeling and myometrial homeostasis in the cycling mouse uterus.iScience · 2023Article
- Epithelial-derived factors induce muscularis mucosa of human induced pluripotent stem cell-derived gastric organoids.Stem cell reports · 2022Article
- Hair follicle stem cells as a skin-organizing signaling center during adult homeostasis.The EMBO journal · 2021Review
- Epithelium-derived Indian Hedgehog restricts stromal expression of ErbB family members that drive colonic tumor cell proliferation.Oncogene · 2021Article
- Hedgehog Signaling in Intestinal Development and Homeostasis.Annual review of physiology · 2021Review
- Hedgehog Signaling in Colorectal Cancer: All in the Stroma?International journal of molecular sciences · 2021Review
- Article
- Tales from the crypt: new insights into intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2019Review
- Signals and forces shaping organogenesis of the small intestine.Current topics in developmental biology · 2019Review
- Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and cancer.Open biology · 2018Review
- Article
- Indian Hedgehog Suppresses a Stromal Cell-Driven Intestinal Immune Response.Cellular and molecular gastroenterology and hepatology · 2018Article
- Chick midgut morphogenesis.The International journal of developmental biology · 2018Review
- YAP/TAZ and Hedgehog Coordinate Growth and Patterning in Gastrointestinal Mesenchyme.Developmental cell · 2017Article
- A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development.PLoS genetics · 2017Article
- Transcriptome of the inner circular smooth muscle of the developing mouse intestine: Evidence for regulation of visceral smooth muscle genes by the hedgehog target gene, cJun.Developmental dynamics : an official publication of the American Association of Anatomists · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The Hedgehog (Hh) pathway plays multiple patterning roles during development of the mammalian gastrointestinal tract, but its role in adult gut function has not been extensively examined. Here we show that chronic reduction in the combined epithelial Indian (Ihh) and Sonic (Shh) hedgehog signal leads to mislocalization of intestinal subepithelial myofibroblasts, loss of smooth muscle in villus cores and muscularis mucosa as well as crypt hyperplasia. In contrast, chronic over-expression of Ihh in the intestinal epithelium leads to progressive expansion of villus smooth muscle, but does not result in reduced epithelial proliferation. Together, these mouse models show that smooth muscle populations in the adult intestinal lamina propria are highly sensitive to the level of Hh ligand. We demonstrate further that Hh ligand drives smooth muscle differentiation in primary intestinal mesenchyme cultures and that cell-autonomous Hh signal transduction in C3H10T1/2 cells activates the smooth muscle master regulator Myocardin (Myocd) and induces smooth muscle differentiation. The rapid kinetics of Myocd activation by Hh ligands as well as the presence of an unusual concentration of Gli sties in this gene suggest that regulation of Myocd by Hh might be direct. Thus, these data indicate that Hh is a critical regulator of adult intestinal smooth muscle homeostasis and suggest an important link between Hh signaling and Myocd activation. Moreover, the data support the idea that lowered Hh signals promote crypt expansion and increased epithelial cell proliferation, but indicate that chronically increased Hh ligand levels do not dampen crypt proliferation as previously proposed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.