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J Cell Biol. 2012 Aug 6;198(3):331-41. doi: 10.1083/jcb.201204086. Epub 2012 Jul 30.

The tumor suppressor Apc controls planar cell polarities central to gut homeostasis.

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1
Laboratoire de Biophotonique et Pharmacologie, Unité Mixte de Recherche 7213, Centre National de la Recherche Scientifique, 67401 Illkirch, France.

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.

PMID:
22851318
PMCID:
PMC3413367
DOI:
10.1083/jcb.201204086
[Indexed for MEDLINE]
Free PMC Article
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