Canonical Wnt signals are essential for homeostasis of the intestinal epithelium
Open accessAbstract
To assess the critical role of Wnt signals in intestinal crypts, we generated transgenic mice ectopically expressing Dickkopf1 (Dkk1), a secreted Wnt inhibitor. We find that epithelial proliferation is greatly reduced coincidentally with the loss of crypts. Although enterocyte differentiation appears unaffected, secretory cell lineages are largely absent. Disrupted intestinal homeostasis is reflected by an absence of nuclear β-catenin, inhibition of c- myc expression, and subsequent up-regulation of p21 CIP1/WAF1 . Thus, our data are the first to establish a direct requirement for Wnt ligands in driving proliferation in the intestinal epithelium, and also define an unexpected role for Wnts in controlling secretory cell differentiation.
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Wnt signaling in the intestinal epithelium is critical for tissue homeostasis in young mice.
“Wnt signaling in the intestinal epithelium is well studied and critical for tissue homeostasis in young mice (Pinto et al., 2003; van der Flier et al., 2009b).”
From Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells (2017) · cites this paper as Pinto et al., 2003
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- Authors
- Pinto, D., Gregorieff, A., Begthel, H., & Clevers, H.
- Affiliations
- Hubrecht Institute for Developmental Biology and Stem Cell Research (NL)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-07-15
- Volume
- 17
- Issue
- 14
- Pages
- 1709-1713
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC196179
- OpenAlex
- W2021370278
- Cited by
- 1,026
- References
- 28
- Citations by year
- 2026: 21 · 2025: 23 · 2024: 40 · 2023: 37 · 2022: 30 · 2021: 51 · 2020: 60 · 2019: 36 · 2018: 55 · 2017: 52 · 2016: 50 · 2015: 48 · 2014: 50 · 2013: 48 · 2012: 52
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- Wnt signaling, intestinal epithelium, intestinal homeostasis, intestinal crypts, DKK1, Wnt inhibitors, epithelial cell proliferation, secretory cell differentiation, β-catenin, c-Myc, p21, enterocytes, transgenic mice
- MeSH terms
- Animals, Cell Division, Cytoskeletal Proteins, Homeostasis, Intestinal Mucosa, Mice, Transgenic, Proteins, Proto-Oncogene Proteins, Signal Transduction, Trans-Activators, Zebrafish Proteins, Intercellular Signaling Peptides and Proteins, Wnt Proteins, beta Catenin, Mice
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