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Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):E8079-E8088. Epub 2016 Nov 28.

Planar cell polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation.

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Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Davis, CA 95616.
Centre de Recherche en Cancérologie de Marseille, Aix-Marseille University, UM105, 3284 Marseille, France.
Paoli Calmettes, UMR7258 CNRS, U1068 INSERM, Cell Polarity, Cell Signalling and Cancer - Equipe Labellisée Ligue Contre le Cancer, F 13009 Marseille, France.
Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702.
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115.
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229;


Blastocyst implantation is a complex process requiring coordination of a dynamic sequence of embryo-uterine interactions. Blood vessels enter the uterus from the mesometrium, demarcating the uterus into mesometrial (M) and antimesometrial (AM) domains. Implantation occurs along the uterine longitudinal axis within specialized implantation chambers (crypts) that originate within the evaginations directed from the primary lumen toward the AM domain. The morphological orientation of crypts in rodent uteri was recognized more than a century ago, but the mechanism remained unknown. Here we provide evidence that planar cell polarity (PCP) signaling orchestrates directed epithelial evaginations to form crypts for implantation in mice. Uterine deletion of Vang-like protein 2, but not Vang-like protein 1, conferred aberrant PCP signaling, misdirected epithelial evaginations, defective crypt formation, and blastocyst attachment, leading to severely compromised pregnancy outcomes. The study reveals a previously unrecognized role for PCP in executing spatial cues for crypt formation and implantation. Because PCP is an evolutionarily conserved phenomenon, our study is likely to inspire implantation studies of this signaling pathway in humans and other species.


PCP; Vangl2; crypt; embryo implantation; uterus

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Conflict of interest statement

The authors declare no conflict of interest.

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