title: Notch and Hippo signaling converge on Strawberry Notch 1 (Sbno1) to synergistically activate Cdx2 during specification of the trophectoderm.
abstract: The first binary cell fate decision occurs at the morula stage and gives rise to two distinct types of cells that constitute the trophectoderm (TE) and inner cell mass (ICM). The cell fate determinant, Cdx2, is induced in TE cells and plays an essential role in their differentiation and maintenance. Notch and Hippo signaling cascades are assumed to converge onto regulatory elements of Cdx2, however, the underlying molecular mechanisms are largely unknown. Here, we show involvement of Strawberry Notch1 (Sbno1), a novel chromatin factor of the helicase superfamily 2, during preimplantation development. Sbno1 knockout embryos die at the preimplantation stage without forming a blastocoel, and Cdx2 is not turned on even though both Yap and Tead4 reside normally in nuclei. Accordingly, Sbno1 acts on the trophectoderm-enhancer (TEE) of Cdx2, ensuring its robust and synergistic activation by the Yap/Tead4 and NICD/Rbpj complexes. Interestingly, this synergism is enhanced when cells are mechanically stretched, which might reflect that TE cells are continuously stretched by the expanding ICM and blastocoel cavity. In addition, the histone chaperone, FACT (FAcilitates Chromatin Transcription) physically interacts with Sbno1. Our data provide new evidence on TE specification, highlighting unexpected but essential functions of the highly conserved chromatin factor, Sbno1.
authors.affiliation: Department of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan.|Department of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan.
authors.forename: Kota Y
authors.initials: KY
authors.lastname: Miyasaka
authors.affiliation: Department of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kubo
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Yasuyuki S
authors.initials: YS
authors.lastname: Kida
authors.affiliation: Department of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawa
authors.affiliation: Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirate
authors.affiliation: Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.|Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 585-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ogura
mesh_terms: D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D001755:Blastocyst / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics*; D000071616:CDX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D004475:Ectoderm / Q000196:embryology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D056488:Histone Chaperones / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D015415:Biomarkers; D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D056488:Histone Chaperones; D051880:Receptors, Notch; D012097:Repressor Proteins; C000629137:Sbno1 protein, mouse