title: Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse.
abstract: In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture. These observations provide insights into the mechanisms of ZGA, and suggest potentials of YAP activators in improving the developmental competence of cultured embryos in assisted human reproduction and animal biotechnology.
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Ji
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Dang
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Sha
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Yuan
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jian-Jie
authors.initials: JJ
authors.lastname: Zhou
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Yan
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Heng-Yu
authors.initials: HY
authors.lastname: Fan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D057809:HEK293 Cells; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins; D015053:Zygote / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008246:Lysophospholipids; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C032881:lysophosphatidic acid