A Dynamic WNT/β-CATENIN Signaling Environment Leads to WNT-Independent and WNT-Dependent Proliferation of Embryonic Intestinal Progenitor Cells. Stem Cell Reports 2016 Nov 08;7(5):826-839
Date
10/11/2016Pubmed ID
27720905Pubmed Central ID
PMC5106483DOI
10.1016/j.stemcr.2016.09.004Scopus ID
2-s2.0-84992065194 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Much of our understanding about how intestinal stem and progenitor cells are regulated comes from studying the late fetal stages of development and the adult intestine. In this light, little is known about intestine development prior to the formation of stereotypical villus structures with columnar epithelium, a stage when the epithelium is pseudostratified and appears to be a relatively uniform population of progenitor cells with high proliferative capacity. Here, we investigated a role for WNT/β-CATENIN signaling during the pseudostratified stages of development (E13.5, E14.5) and following villus formation (E15.5) in mice. In contrast to the well-described role for WNT/β-CATENIN signaling as a regulator of stem/progenitor cells in the late fetal and adult gut, conditional epithelial deletion of β-catenin or the Frizzled co-receptors Lrp5 and Lrp6 had no effect on epithelial progenitor cell proliferation in the pseudostratified epithelium. Mutant embryos displayed obvious developmental defects, including loss of proliferation and disruptions in villus formation starting only at E15.5. Mechanistically, our data suggest that WNT signaling-mediated proliferation at the time of villus formation is driven by mesenchymal, but not epithelial, WNT ligand secretion.
Author List
Chin AM, Tsai YH, Finkbeiner SR, Nagy MS, Walker EM, Ethen NJ, Williams BO, Battle MA, Spence JRMESH terms used to index this publication - Major topics in bold
AnimalsCell Death
Cell Differentiation
Cell Proliferation
Embryonic Stem Cells
Gene Expression
Intestinal Mucosa
Intestines
Low Density Lipoprotein Receptor-Related Protein-5
Low Density Lipoprotein Receptor-Related Protein-6
Mice
Mice, Transgenic
Morphogenesis
Myocytes, Smooth Muscle
Organogenesis
Receptor, Platelet-Derived Growth Factor alpha
SOX9 Transcription Factor
Wnt Proteins
Wnt Signaling Pathway
beta Catenin
