title: Deficiency in Crumbs homolog 2 (Crb2) affects gastrulation and results in embryonic lethality in mice.
abstract: The Crumbs family of transmembrane proteins has an important role in the differentiation of the apical membrane domain in various cell types, regulating such processes as epithelial cell polarization. The mammalian Crumbs protein family is composed of three members. Here, we inactivated the mouse Crb2 gene with gene-targeting techniques and found that the protein is crucial for early embryonic development with severe abnormalities appearing in Crb2-deficient embryos at late-gastrulation. Our findings indicate that the primary defect in the mutant embryos is disturbed polarity of the epiblast cells at the primitive streak, which affects epithelial to mesenchymal transition (EMT) during gastrulation, resulting in impaired mesoderm and endoderm formation, and embryonic lethality by embryonic day 12.5. These findings therefore indicate a novel role for the Crumbs family of proteins.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Division of Matrix Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Xiao
authors.forename: Jaakko
authors.initials: J
authors.lastname: Patrakka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nukui
authors.forename: Lijun
authors.initials: L
authors.lastname: Chi
authors.forename: Dadi
authors.initials: D
authors.lastname: Niu
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: Timo
authors.initials: T
authors.lastname: Pikkarainen
authors.forename: Timo
authors.initials: T
authors.lastname: Pikkarainan
authors.forename: Seppo
authors.initials: S
authors.lastname: Vainio
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004707:Endoderm / Q000196:embryology* / Q000648:ultrastructure; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D054262:Gastrulation / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008648:Mesoderm / Q000196:embryology* / Q000648:ultrastructure; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: C568885:Crb2 protein, mouse; D008565:Membrane Proteins