title: Molecular identification of t(w5): Vps52 promotes pluripotential cell differentiation through cell-cell interactions.
abstract: After implantation, pluripotent epiblasts are converted to embryonic ectoderm through cell-cell interactions that significantly change the transcriptional and epigenetic networks. An entrée to understanding this vital developmental transition is the t(w5) mutation of the mouse t complex. This mutation produces highly specific defects in the embryonic ectoderm before gastrulation, leading to death of the embryonic ectoderm. Using a positional cloning approach, we have now identified the mutated gene, completing a decades-long search. The gene, vacuolar protein sorting 52 (Vps52), is a mouse homolog of yeast VPS52 that is involved in the retrograde trafficking of endosomes. Our data suggest that Vps52 acts in extraembryonic tissues to support the growth and differentiation of embryonic ectoderm via cell-cell interactions. It is also required in the formation of embryonic structures at a later stage of development, revealing hitherto unknown functions of Vps52 in the development of a multicellular organism.
authors.affiliation: Technology and Development Team for Mammalian Cellular Dynamics, RIKEN BioResource Center, Tsukuba, Ibaraki 305-00074, Japan.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Masayo
authors.initials: M
authors.lastname: Kondo
authors.forename: Michiko
authors.initials: M
authors.lastname: Hirose
authors.forename: Misao
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Mekada
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Takagi
authors.forename: Karen
authors.initials: K
authors.lastname: Artzt
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D001483:Base Sequence; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D004475:Ectoderm / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005091:Exons; D016368:Frameshift Mutation; D006239:Haplotypes; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008938:Mitosis; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins; D056427:t-Complex Genome Region
chemical_list: D011506:Proteins; D033921:Vesicular Transport Proteins; C485462:Vps52 protein, mouse