title: Oct4 cell-autonomously promotes primitive endoderm development in the mouse blastocyst.
abstract: In embryonic stem (ES) cells and in early mouse embryos, the transcription factor Oct4 is an essential regulator of pluripotency. Oct4 transcriptional targets have been described in ES cell lines; however, the molecular mechanisms by which Oct4 regulates establishment of pluripotency in the epiblast (EPI) have not been fully elucidated. Here, we show that neither maternal nor zygotic Oct4 is required for the formation of EPI cells in the blastocyst. Rather, Oct4 is first required for development of the primitive endoderm (PE), an extraembryonic lineage. EPI cells promote PE fate in neighboring cells by secreting Fgf4, and Oct4 is required for expression of Fgf4, but we show that Oct4 promotes PE development cell-autonomously, downstream of Fgf4 and Mapk. Finally, we show that Oct4 is required for the expression of multiple EPI and PE genes as well as multiple metabolic pathways essential for the continued growth of the preimplantation embryo.
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
authors.forename: Tristan
authors.initials: T
authors.lastname: Frum
authors.forename: Michael A
authors.initials: MA
authors.lastname: Halbisen
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Wang
authors.forename: Hossein
authors.initials: H
authors.lastname: Amiri
authors.forename: Paul
authors.initials: P
authors.lastname: Robson
authors.forename: Amy
authors.initials: A
authors.lastname: Ralston
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001755:Blastocyst / Q000166:cytology / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D004707:Endoderm / Q000166:cytology / Q000196:embryology*; D005260:Female; D051519:Fibroblast Growth Factor 4 / Q000502:physiology; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy
chemical_list: C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse