title: Nepro is localized in the nucleolus and essential for preimplantation development in mice.
abstract: We generated knockout (KO) mice of Nepro, which has been shown to be necessary to maintain neural progenitor cells downstream of Notch in the mouse developing neocortex by using knockdown experiments, to explore its function in embryogenesis. Nepro KO embryos were morphologically indistinguishable from wild type (WT) embryos until the morula stage but failed in blastocyst formation, and many cells of the KO embryos resulted in apoptosis. We found that Nepro was localized in the nucleolus at the blastocyst stage. The number of nucleolus precursor bodies (NPBs) and nucleoli per nucleus was significantly higher in Nepro KO embryos compared with WT embryos later than the 2-cell stage. Furthermore, at the morula stage, whereas 18S rRNA and ribosomal protein S6 (rpS6), which are components of the ribosome, were distributed to the cytoplasm in WT embryos, they were mainly localized in the nucleoli in Nepro KO embryos. In addition, in Nepro KO embryos, the amount of the mitochondria-associated p53 protein increased, and Cytochrome c was distributed in the cytoplasm. These findings indicate that Nepro is a nucleolus-associated protein, and its loss leads to the apoptosis before blastocyst formation in mice.
authors.affiliation: Department of Developmental Biology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Developmental Biology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Developmental Biology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Muroyama
authors.affiliation: Biomedical Research Center, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Lisa
authors.initials: L
authors.lastname: Fujimura
authors.affiliation: Biomedical Research Center, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.|Department of Biomedical Science, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.affiliation: Department of Developmental Biology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D017209:Apoptosis; D001755:Blastocyst / Q000378:metabolism*; D002466:Cell Nucleolus / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D012097:Repressor Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: C545717:Nepro protein, mouse; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins
keywords: Nepro; Notch; nucleolus; preimplantation development; ribosome biogenesis