Planar cell polarity signaling in the uterus directs appropriate positioning of the Crypt for Embryo implantation

Jia Yuan, Jeeyeon Cha, Wenbo Deng, Amanda Bartos, Xiaofei Sun, Hsin-Yi Henry Ho, Jean Paul Borg, Terry P. Yamaguchi, Yingzi Yang, Sudhansu K. Dey, R. Michael Roberts

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E8079-E8088
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number50
DOIs
StatePublished - Dec 13 2016

Keywords

  • Crypt
  • Embryo implantation
  • PCP
  • Uterus
  • Vangl2

ASJC Scopus subject areas

  • General

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