PMID- 12865297 OWN - NLM STAT- MEDLINE DCOM- 20030808 LR - 20250214 IS - 0890-9369 (Print) IS - 0890-9369 (Linking) VI - 17 IP - 14 DP - 2003 Jul 15 TI - Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. PG - 1709-13 AB - 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. FAU - Pinto, Daniel AU - Pinto D AD - Netherlands Institute for Developmental Biology, Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. FAU - Gregorieff, Alex AU - Gregorieff A FAU - Begthel, Harry AU - Begthel H FAU - Clevers, Hans AU - Clevers H LA - eng PT - Journal Article PL - United States TA - Genes Dev JT - Genes & development JID - 8711660 RN - 0 (CTNNB1 protein, mouse) RN - 0 (Cytoskeletal Proteins) RN - 0 (Dkk1 protein, mouse) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Trans-Activators) RN - 0 (Wnt Proteins) RN - 0 (Zebrafish Proteins) RN - 0 (beta Catenin) RN - 0 (dkk1b protein, zebrafish) SB - IM MH - Animals MH - Cell Division/physiology MH - Cytoskeletal Proteins/metabolism MH - Homeostasis/*physiology MH - Intercellular Signaling Peptides and Proteins MH - Intestinal Mucosa/*metabolism MH - Mice MH - Mice, Transgenic MH - Proteins/metabolism MH - Proto-Oncogene Proteins/*metabolism MH - Signal Transduction/*physiology MH - Trans-Activators/metabolism MH - Wnt Proteins MH - *Zebrafish Proteins MH - beta Catenin PMC - PMC196179 EDAT- 2003/07/17 05:00 MHDA- 2003/08/09 05:00 PMCR- 2004/01/15 CRDT- 2003/07/17 05:00 PHST- 2003/07/17 05:00 [pubmed] PHST- 2003/08/09 05:00 [medline] PHST- 2003/07/17 05:00 [entrez] PHST- 2004/01/15 00:00 [pmc-release] AID - 17/14/1709 [pii] AID - 0171709 [pii] AID - 10.1101/gad.267103 [doi] PST - ppublish SO - Genes Dev. 2003 Jul 15;17(14):1709-13. doi: 10.1101/gad.267103.