title: External mechanical cues trigger the establishment of the anterior-posterior axis in early mouse embryos.
abstract: Mouse anterior-posterior axis polarization is preceded by formation of the distal visceral endoderm (DVE) by unknown mechanisms. Here, we show by in vitro culturing of embryos immediately after implantation in microfabricated cavities that the external mechanical cues exerted on the embryo are crucial for DVE formation, as well as the elongated egg cylinder shape, without affecting embryo-intrinsic transcriptional programs except those involving DVE-specific genes. This implies that these developmental events immediately after implantation are not simply embryo-autonomous processes but require extrinsic factors from maternal tissues. Moreover, the mechanical forces induce a breach of the basement membrane barrier at the distal portion locally, and thereby the transmigrated epiblast cells emerge as the DVE cells. Thus, we propose that external mechanical forces exerted by the interaction between embryo and maternal uterine tissues directly control the location of DVE formation at the distal tip and consequently establish the mammalian primary body axis.
authors.affiliation: Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan; Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hiramatsu
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Matsuoka
authors.affiliation: Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kimura-Yoshida
authors.affiliation: Department of Biomechanics, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo, Kyoto 606-8507, Japan.
authors.forename: Sung-Woong
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Mochida
authors.affiliation: Department of Biomechanics, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo, Kyoto 606-8507, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takayama
authors.affiliation: Department of Molecular Embryology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan; Department of Pediatric and Neonatal-Perinatal Research, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: imatsuo@mch.pref.osaka.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsuo
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D019521:Body Patterning / Q000235:genetics*; D002465:Cell Movement; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000378:metabolism*; D004707:Endoderm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic