Canonical Wnt signals are essential for homeostasis of the intestinal epithelium.

By Daniel Pinto, A. Gregorieff, H. Begthel, Hans Clevers. Genes & Development, 2003

1,105 citations recorded by the source corpus.

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 beta-catenin, inhibition of c-myc expression, and subsequent up-regulation of p21CIP1/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.

Subfields: Genetics, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/36ab8c7f4c5e0c3027056037c367703e18f48f6e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Hans Clevers
2. Nick Barker
3. Elaine Fuchs
4. C. Blanpain
5. K. Willert
6. K. Jones
7. A. Gregorieff
8. V. Horsley

In Molecular Biology

1. Hans Clevers
2. C. Blanpain
3. Elaine Fuchs
4. Nick Barker
5. V. Horsley
6. K. Willert
7. K. Jones
8. Alexander van Oudenaarden

In Surgery

1. Hans Clevers
2. W. de Lau
3. P. Gros
4. W. Peng
5. Elaine Fuchs
6. C. Blanpain
7. V. Horsley

Citations in the corpus

• Wnt signaling: is the party in the nucleus? (2006, background): “components results in depletion of intestinal crypt stem cells and loss of proliferative epithelial cells (Pinto et al. 2003; Kuhnert et al. 2004).”
• Wnt signaling in development and tissue homeostasis (2018, background): “…have shown that the disruption of Tcf4 (Korinek et al., 1998) or β -catenin (Fevr et al., 2007), or the overexpression of Dkk1 (Fevr et al., 2007; Pinto et al., 2003), leads to robust loss of transit amplifying cells and crypt structures, confirming the functional requirement of Wnt-β -catenin…”
• SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes (2004, background): “In addition, Wnt signals control the differentiation of the secretory cell lineage of the epithelium, because overexpression of the Wnt-pathway inhibitor Dickkopf1 blocks differentiation of the Paneth, goblet, and enteroendocrine cell types (Pinto et al., 2003).”
• The intestinal crypt, a prototype stem cell compartment. (2013, background): “Maintenance of adult crypt proliferation continues to be dependent on Wnt, as demonstrated upon transgenic expression of the Wnt receptor antagonist Dkk1 (Pinto et al., 2003) and upon conditional 154, July 18, 2013 ª2013 Elsevier Inc. 275 (A) Hand-drawn crypt (Paneth, 1887).”