Placental labyrinth formation in mice requires endothelial FLRT2/UNC5B signaling

Ikue Tai-Nagara, Yusuke Yoshikawa, Naoko Numata, Tomofumi Ando, Keisuke Okabe, Yuki Sugiura, Masaki Ieda, Nobuyuki Takakura, Osamu Nakagawa, Bin Zhou, Koji Okabayashi, Makoto Suematsu, Yuko Kitagawa, Martin Bastmeyer, Kohji Sato, Rüdiger Klein, Sutip Navankasattusas, Dean Y. Li, Satoru Yamagishi, Yoshiaki Kubota

研究成果: Article査読

18 被引用数 (Scopus)


The placental labyrinth is the interface for gas and nutrient exchange between the embryo and the mother; hence its proper development is essential for embryogenesis. However, the molecular mechanism underlying development of the placental labyrinth, particularly in terms of its endothelial organization, is not well understood. Here, we determined that fibronectin leucine-rich transmembrane protein 2 (FLRT2), a repulsive ligand of the UNC5 receptor family for neurons, is unexpectedly expressed in endothelial cells specifically in the placental labyrinth. Mice lacking FLRT2 in endothelial cells exhibited embryonic lethality at mid-gestation, with systemic congestion and hypoxia. Although they lacked apparent deformities in the embryonic vasculature and heart, the placental labyrinths of these embryos exhibited aberrant alignment of endothelial cells, which disturbed the feto-maternal circulation. Interestingly, this vascular deformity was related to endothelial repulsion through binding to the UNC5B receptor. Our results suggest that the proper organization of the placental labyrinth depends on coordinated inter-endothelial repulsion, which prevents uncontrolled layering of the endothelium.

ジャーナルDevelopment (Cambridge)
出版ステータスPublished - 2017

ASJC Scopus subject areas

  • 分子生物学
  • 発生生物学


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