title: Platypus Pou5f1 reveals the first steps in the evolution of trophectoderm differentiation and pluripotency in mammals.
abstract: Uterine nourishment of embryos by the placenta is a key feature of mammals. Although a variety of placenta types exist, they are all derived from the trophectoderm (TE) cell layer of the developing embryo. Egg-laying mammals (platypus and echidnas) are distinguished by a very short intrauterine embryo development, in which a simple placenta forms from TE-like cells. The Pou5f1 gene encodes a class V POU family transcription factor Oct3/4. In mice, Oct3/4 together with the highly conserved caudal-related homeobox transcription factor Cdx2, determines TE fate in pre-implantation development. In contrast to Cdx2, Pou5f1 has only been identified in eutherian mammals and marsupials, whereas, in other vertebrates, pou2 is considered to be the Pou5f1 ortholog. Here, we show that platypus and opossum genomes contain a Pou5f1 and pou2 homolog, pou2-related, indicating that these two genes are paralogues and arose by gene duplication in early mammalian evolution. In a complementation assay, we found that platypus or human Pou5f1, but not opossum or zebrafish pou2, restores self-renewal in Pou5f1-null mouse ES cells, showing that platypus possess a fully functional Pou5f1 gene. Interestingly, we discovered that parts of one of the conserved regions (CR4) is missing from the platypus Pou5f1 promoter, suggesting that the autoregulation and reciprocal inhibition between Pou5f1 and Cdx2 evolved after the divergence of monotremes and may be linked to the development of more elaborate placental types in marsupial and eutherian mammals.
authors.affiliation: Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology (CDB), 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 6500047, Japan. niwa@cdb.riken.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niwa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sekita
authors.forename: Enkhjargal
authors.initials: E
authors.lastname: Tsend-Ayush
authors.forename: Frank
authors.initials: F
authors.lastname: Grützner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002454:Cell Differentiation; D004475:Ectoderm; D053595:Embryonic Stem Cells; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D008322:Mammals / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D050809:POU Domain Factors / Q000235:genetics; D010920:Placenta / Q000166:cytology* / Q000196:embryology; D010987:Platypus / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment
chemical_list: D050814:Octamer Transcription Factor-3; D050809:POU Domain Factors