title: Planar cell polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation.
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.
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors.forename: Jia
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors.forename: Jeeyeon
authors.initials: J
authors.lastname: Cha
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Deng
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors.forename: Amanda
authors.initials: A
authors.lastname: Bartos
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Davis, CA 95616.
authors.forename: Hsin-Yi Henry
authors.initials: HH
authors.lastname: Ho
authors.affiliation: 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.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Yamaguchi
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; sk.dey@cchmc.org.
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D000072261:Dishevelled Proteins / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology*; D004848:Epithelium / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D011256:Pregnancy Outcome; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014599:Uterus / Q000033:anatomy & histology / Q000502:physiology*; D000071818:Wnt-5a Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D002352:Carrier Proteins; D000072261:Dishevelled Proteins; D009419:Nerve Tissue Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D000071818:Wnt-5a Protein; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C000606582:Dvl2 protein, mouse; C431577:Ltap protein, mouse; C438615:Wnt5a protein, mouse
keywords: PCP; Vangl2; crypt; embryo implantation; uterus