title: The tumor suppressor Apc controls planar cell polarities central to gut homeostasis.
abstract: The stem cells (SCs) at the bottom of intestinal crypts tightly contact niche-supporting cells and fuel the extraordinary tissue renewal of intestinal epithelia. Their fate is regulated stochastically by populational asymmetry, yet whether asymmetrical fate as a mode of SC division is relevant and whether the SC niche contains committed progenitors of the specialized cell types are under debate. We demonstrate spindle alignments and planar cell polarities, which form a novel functional unit that, in SCs, can yield daughter cell anisotropic movement away from niche-supporting cells. We propose that this contributes to SC homeostasis. Importantly, we demonstrate that some SC divisions are asymmetric with respect to cell fate and provide data suggesting that, in some SCs, mNumb displays asymmetric segregation. Some of these processes were altered in apparently normal crypts and microadenomas of mice carrying germline Apc mutations, shedding new light on the first stages of progression toward colorectal cancer.
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, Unité Mixte de Recherche 7213, Centre National de la Recherche Scientifique, 67401 Illkirch, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Bellis
authors.forename: Isabelle
authors.initials: I
authors.lastname: Duluc
authors.forename: Béatrice
authors.initials: B
authors.lastname: Romagnolo
authors.forename: Christine
authors.initials: C
authors.lastname: Perret
authors.forename: Maree C
authors.initials: MC
authors.lastname: Faux
authors.forename: Denis
authors.initials: D
authors.lastname: Dujardin
authors.forename: Caroline
authors.initials: C
authors.lastname: Formstone
authors.forename: Sally
authors.initials: S
authors.lastname: Lightowler
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ramsay
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Freund
authors.forename: Jan R
authors.initials: JR
authors.lastname: De Mey
mesh_terms: D000199:Actins / Q000737:chemistry; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D016880:Anisotropy; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry; D003433:Crosses, Genetic; D018450:Disease Progression; D004285:Dogs; D006706:Homeostasis; D007399:Interphase; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D009154:Mutation; D013269:Stochastic Processes; D013692:Telophase
chemical_list: D000199:Actins; D025601:Adenomatous Polyposis Coli Protein; D002843:Chromatin