R-spondin3 is required for mouse placental development

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.08.018 Byline: Motoko Aoki (a)(c), Michihiro Mieda (a), Toshio Ikeda (b), Yoshio Hamada (d), Harukazu Nakamura (c), Hitoshi Okamoto (a)(e) Keywords: R-spondin; Labyrinth; Placental development; Glial cells missing gene Abstract: Mouse R-spondin3 (Rspo3) is a member of the R-spondin protein family, which is characterized by furin-like cysteine-rich domains and a thrombospondin type 1 repeat. Rspo3 has been proposed to function as a secretory molecule that promotes the Wnt/[beta]-catenin signaling pathway. We generated mice bearing a mutant Rspo3 allele in which a lacZ-coding region replaced the coding region of the first exon. The homozygous mutant mice died at about embryonic day 10, due to impaired formation of the labyrinthine layer of the placenta. Rspo3 was expressed in the allantoic component of the labyrinth. In the homozygous mutant placentas, fetal blood vessels did not penetrate into the chorion, and expression of Gcm1, encoding the transcription factor glial cells missing-1 (Gcm1), was dramatically reduced in the chorionic trophoblast cells. These findings suggest a critical role for Rspo3 in the interaction between chorion and allantois in labyrinthine development. Author Affiliation: (a) Laboratory for Developmental Gene Regulation, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan (b) Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan (c) Department of Molecular Neurobiology, Graduate School of Life Sciences, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan (d) National Institute for Basic Biology, Okazaki, Aichi 444-8585, Japan (e) Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan Article History: Received 12 April 2006; Revised 2 August 2006; Accepted 7 August 2006