title: Implication of MEK1 and MEK2 in the establishment of the blood-placenta barrier during placentogenesis in mouse.
abstract: The ERK/MAPK signalling cascade is involved in many cellular functions. In mice, the targeted ablation of genes coding for members of this pathway is often associated with embryonic death due to the abnormal development of the placenta. The placenta is essential for nutritional and gaseous exchanges between maternal and embryonic circulations, as well as for the elimination of metabolic waste. These exchanges occur without direct contact between the two circulations. In mice, the blood-placenta barrier consists of a triple layer of trophoblast cells adjacent to endothelial cells from the embryo. In the ERK/MAPK cascade, MEK1 and MEK2 are dual-specificity kinases responsible for the activation of the ERK1 and ERK2 kinases. Inactivation of Mek1 causes placental malformations resulting from defective proliferation and differentiation of the labyrinthine trophoblast cells and leading to a severe delay in the development and the vascularization of the placenta, which explains the embryonic death. Although Mek2(-/-) mutants survive without any apparent phenotype, a large proportion of Mek1(+/-)Mek2(+/-) double heterozygous mutants die during gestation from placenta anomalies affecting the establishment of the blood-placenta barrier. Together, these data reveal how crucial is the role of the ERK/MAPK pathway during the formation of the placenta.
authors.affiliation: Centre de recherche en cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Canada. jean.charron@crhdq.ulaval.ca
authors.forename: Jean
authors.initials: J
authors.lastname: Charron
authors.forename: Vickram
authors.initials: V
authors.lastname: Bissonauth
authors.forename: Valérie
authors.initials: V
authors.lastname: Nadeau
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D047495:PPAR gamma / Q000502:physiology; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy
chemical_list: D004268:DNA-Binding Proteins; D047495:PPAR gamma; C094751:Ubp1 protein, mouse; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482127:Map2k1 protein, mouse; C482129:Map2k2 protein, mouse