EphB receptors coordinate migration and proliferation in the intestinal stem cell niche.
More than 10(10) cells are generated every day in the human intestine. Wnt proteins are key regulators of proliferation and are known endogenous mitogens for intestinal progenitor cells. The positioning of cells within the stem cell niche in the intestinal epithelium is controlled by B subclass ephrins through their interaction with EphB receptors. We report that EphB receptors, in addition to directing cell migration, regulate proliferation in the intestine. EphB signaling promotes cell-cycle reentry of progenitor cells and accounts for approximately 50% of the mitogenic activity in the adult mouse small intestine and colon. These data establish EphB receptors as key coordinators of migration and proliferation in the intestinal stem cell niche.
Holmberg
Johan
J
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Genander
Maria
M
Halford
Michael M
MM
Annerén
Cecilia
C
Sondell
Mariann
M
Chumley
Michael J
MJ
Silvany
Robert E
RE
Henkemeyer
Mark
M
Frisén
Jonas
J
D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D003106:Colon / Q000166:cytology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D036183:Receptor, EphB2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D036223:Receptor, EphB3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D051153:Wnt Proteins / Q000502:physiology
D051153:Wnt Proteins; D036183:Receptor, EphB2; D036223:Receptor, EphB3