title: Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development.
abstract: The maternal nucleolus is required for proper activation of the embryonic genome (EGA) and early embryonic development. Nucleologenesis is characterized by the transformation of a nucleolar precursor body (NPB) to a mature nucleolus during preimplantation development. However, the function of NPBs and the involved molecular factors are unknown. We uncover a novel role for the pluripotency factor LIN28, the biological significance of which was previously demonstrated in the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells. Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28 protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28 morpholino, the majority of embryos arrest between the 2- and 4-cell stages and never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB sites, indicating that functional NPBs were not assembled. Based on these results, we propose that LIN28 is an essential factor of nucleologenesis during early embryonic development.
authors.affiliation: German Primate Center, Stem Cell Biology Unit, Kellnerweg 4, 37077 Goettingen, Germany. evogt@gwdg.de
authors.forename: Edgar J
authors.initials: EJ
authors.lastname: Vogt
authors.forename: Maciej
authors.initials: M
authors.lastname: Meglicki
authors.forename: Kristina Ilka
authors.initials: KI
authors.lastname: Hartung
authors.forename: Ewa
authors.initials: E
authors.lastname: Borsuk
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Behr
mesh_terms: D000818:Animals; D002144:Callithrix; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D000090243:Nucleophosmin; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C488352:Lin-28 protein, mouse; C000715570:Npm1 protein, mouse; D016601:RNA-Binding Proteins; D000090243:Nucleophosmin