title: Wnt secretion from epithelial cells and subepithelial myofibroblasts is not required in the mouse intestinal stem cell niche in vivo.
abstract: Wnt signaling is a crucial aspect of the intestinal stem cell niche required for crypt cell proliferation and differentiation. Paneth cells or subepithelial myofibroblasts are leading candidate sources of the required Wnt ligands, but this has not been tested in vivo. To abolish Wnt-ligand secretion, we used Porcupine (Porcn) conditional-null mice crossed to strains expressing inducible Cre recombinase in the epithelium, including Paneth cells (Villin-Cre (ERT2) ); in smooth muscle, including subepithelial myofibroblasts (Myh11-Cre (ERT2) ); and simultaneously in both compartments. Elimination of Wnt secretion from any of these compartments did not disrupt tissue morphology, cell proliferation, differentiation, or Wnt pathway activity. Thus, Wnt-ligand secretion from these cell populations is dispensable for intestinal homeostasis, revealing that a minor cell type or significant and unexpected redundancy is responsible for physiologic Wnt signaling in vivo.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA ; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02215, USA.
authors: Adrianna K
authors: AK
authors: San Roman
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors: Chenura D
authors: CD
authors: Jayewickreme
authors: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors: L Charles
authors: LC
authors: Murtaugh
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA ; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
authors: Ramesh A
authors: RA
authors: Shivdasani
mesh_terms: D000217:Acyltransferases; D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D018390:Gene Targeting; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000166:cytology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism*; D055153:Stem Cell Niche; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D008565:Membrane Proteins; D051153:Wnt Proteins; D000217:Acyltransferases; C491187:Porcn protein, mouse