title: Cloning of complementary DNAs encoding structurally related homeoproteins from preimplantation mouse embryos: their involvement in the differentiation of embryonic stem cells.
abstract: During the preimplantation development of mouse embryos between the 4-cell to 8-cell stage and the morula stage, when the first irreversible segregation of cell fates proceeds into the pluripotent inner cell mass (progenitor cells to form the fetus) and the trophectoderm (to form the placenta) of blastocysts, pluripotency-maintaining and differentiation-inducing genes are expressed to coordinately regulate cell fates. Three structurally related cDNAs (Crxos1, Crxos1 sv2, and Crxos1 tv3) that exhibited concomitant elevated expression during this critical period were identified by subtractive cDNA cloning. CRXOS1 contains two homeodomains, while CRXOS1 sv2 and CRXOS1 tv3 each contain one of the homeodomains included in CRXOS1. Crxos1, Crxos1 sv2, and Crxos1 tv3 were expressed differentially during in vitro embryonic stem (ES) cell differentiation. Even under differentiation-inducing conditions, forced expression of Crxos1 sv2 inhibited the differentiation of ES cells. In contrast, under conditions that promote self-renewal of ES cells, forced expression of Crxos1 induced differentiation. Forced expression of Crxos1 resulted in induction of Gata4 but in repression of T, probably indicating that Crxos1 promotes the differentiation of ES cells into primitive endoderm, while inhibiting differentiation into mesoderm. On the other hand, no apparent effects of forced expression of Crxos1 tv3 were observed. Taken together, it was concluded that these transcripts encoding homeoproteins are capable of regulating the maintenance and/or differentiation of mouse ES cells and likely regulate that of preimplantation embryos.
authors.affiliation: Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Saito
authors.forename: Hajime
authors.initials: H
authors.lastname: Abe
authors.forename: Masato
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Emiko
authors.initials: E
authors.lastname: Irokawa
authors.forename: Masafumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hosoi
authors.forename: Miki
authors.initials: M
authors.lastname: Soma
authors.forename: Kano
authors.initials: K
authors.lastname: Kasuga
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kojima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D019556:COS Cells; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification* / Q000378:metabolism; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011247:Pregnancy; D017385:Sequence Homology
chemical_list: D018076:DNA, Complementary; D018398:Homeodomain Proteins