Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Microarray analysis of gene expression profiles in Map2k1+/-Map2k2+/- and Map2k1flox/-Map2k2+/-Tg+/Sox2Cre placentas

ABSTRACT: The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, encoding dual-specificity kinases responsible for ERK/MAP kinase activation. Loss of Map2k1 function in mouse causes embryonic lethality due to placental defects, while Map2k2 mutant mice survive with a normal lifespan. The Map2k1 mutation interferes with the growth of the labyrinthine region of the placenta and its vascularization. Map2k1+/-Map2k2+/- embryos also die during gestation of underdevelopment of the labyrinth. In Map2k1+/-Map2k2+/- mutants, the vascularization of the labyrinth is reduced and defects in SynT-II formation lead to the accumulation of multinucleated trophoblasts giant cells (MTG). Deletion of both Map2k1 alleles in allantoïs-derived tissues in Map2k1+/ Map2k2+/- placenta (Map2k1flox/-Map2k2+/-Tg+/Sox2Cre) increases the penetrance and the expressivity of the MTG placental phenotype. Microarray analysis with RNA extracted from placentas of E12.5 wt, Map2k1+/-Map2k2+/- and Map2k1flox/-Map2k2+/-Tg+/Sox2Cre embryos was performed to evaluate the molecular impact of the loss of Map2k alleles on placenta development. Total RNA was isolated from placentas of E12.5 Map2k1+/+Map2k2+/+(control), from E12.5 Map2k1+/-Map2k2+/- embryos (experimental) and from E12.5 and Map2k1flox/-Map2k2+/-Tg+/Sox2Cre embryos (experimental). Four specimens were analyzed per genotype.

ORGANISM(S): Mus musculus

SUBMITTER: Eric Paquet

PROVIDER: E-GEOD-51644 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Essential role of the ERK/MAPK pathway in blood-placental barrier formation.

Nadeau Valérie V Charron Jean J

Development (Cambridge, England) 20140619 14

The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, which encode dual-specificity kinases responsible for ERK activation. Loss of Map2k1 function in mouse causes embryonic lethality due to placental defects, whereas Map2k2 mutants have a normal lifespan. The majority of Map2k1(+/-) Map2k2(+/-) embryos die during gestation from the underdevelopment of the placenta labyrinth, demonstrating that both kinases are involved in placenta formation. Map2k1(+/-) Map2k2(+/-) m ...[more]

PMID: 24948605

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Project description:Healthy placental development is essential for reproductive success; failure of the feto-maternal interface results in preeclampsia and intrauterine growth retardation. We found that grainyhead-like 2 (GRHL2), a CP2-type transcription factor, is highly expressed in chorionic trophoblast cells, including basal chorionic trophoblast (BCT) cells located at the chorioallantoic interface in murine placentas. Placentas from Grhl2-deficient mouse embryos displayed defects in BCT cell polarity and basement membrane integrity at the chorioallantoic interface, as well as a severe disruption of labyrinth branchingmorphogenesis.Selective Grhl2 inactivation only in epiblastderived cells rescued all placental defects but phenocopied intraembryonic defects observed in global Grhl2 deficiency, implying the importance of Grhl2 activity in trophectoderm-derived cells. ChIPseq identified 5282 GRHL2 binding sites in placental tissue. By integrating these data with placental gene expression profiles, we identified direct and indirect Grhl2 targets and found a marked enrichment of GRHL2 binding adjacent to genes downregulated in Grhl2−/− placentas, which encoded known regulators of placental development and epithelial morphogenesis. These genes included that encoding the serine protease inhibitor Kunitz type 1 (Spint1), which regulates BCT cell integrity and labyrinth formation. In human placenta, we found that human orthologs of murine GRHL2 and its targets displayed co-regulation and were expressed in trophoblast cells in a similar domain as in mouse placenta. Our data indicate that a conserved Grhl2-coordinated gene network controls trophoblast branching morphogenesis, thereby facilitating development of the site of feto-maternal exchange. This might have implications for syndromes related to placental dysfunction. In vivo genome-wide examination of binding sites of the transcription factor GRHL2 by ChIP-seq using wild-type murine E17.5 placenta tissue. Two samples in total: one GRHL2 ChIP sample and one IgG ChIP sample using wild-type placentas tissue as antibody control.

Dataset Information

Microarray analysis of gene expression profiles in Map2k1+/-Map2k2+/- and Map2k1flox/-Map2k2+/-Tg+/Sox2Cre placentas

Publications

Essential role of the ERK/MAPK pathway in blood-placental barrier formation.

Similar Datasets

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