Conditional knock-out reveals that zygotic vezatin-null mouse embryos die at implantation.
Vezatin, a protein associated to adherens junctions in epithelial cells, is already expressed in mouse oocytes and during pre-implantation development. Using a floxed strategy to generate a vezatin-null allele, we show that the lack of zygotic vezatin is embryonic lethal, indicating that vezatin is an essential gene. Homozygous null embryos are able to elicit a decidual response but as early as day 6.0 post-coitum mutant implantation sites are devoid of embryonic structures. Mutant blastocysts are morphologically normal, but only half of them are able to hatch upon in vitro culture and the blastocyst outgrowths formed after 3.5 days in culture exhibit severe abnormalities, in particular disrupted intercellular adhesion and clear signs of cellular degeneration. Notably, the junctional proteins E-cadherin and beta-catenin are delocalized and not observed at the plasma membrane anymore. These in vitro observations reinforce the idea that homozygous vezatin-null mutants die at the time of implantation because of a defect in intercellular adhesion. Together these results indicate that the absence of zygotic vezatin is deleterious for the implantation process, most likely because cadherin-dependent intercellular adhesion is impaired in late blastocysts when the maternal vezatin is lost.
Hyenne
Vincent
V
Biologie cellulaire du Développement, CNRS UMR 7622, Université Pierre et Marie Curie, 9 Quai St Bernard, 75252 Paris cedex 05, France.
Souilhol
Céline
C
Cohen-Tannoudji
Michel
M
Cereghini
Silvia
S
Petit
Christine
C
Langa
Francina
F
Maro
Bernard
B
Simmler
Marie-Christine
MC
D022005:Adherens Junctions / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010064:Embryo Implantation / Q000235:genetics*; D004622:Embryo, Mammalian / Q000737:chemistry / Q000502:physiology*; D005804:Genes, Lethal; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015053:Zygote / Q000737:chemistry / Q000502:physiology*
D002352:Carrier Proteins; D008565:Membrane Proteins; C506603:vezatin protein, mouse