| Experiment Id | E-GEOD-21954 | Series Id | GSE21954 |
| Name | Nucleoredoxin is required for the maintenance of Wnt/beta-catenin signaling in mice embryo | Experiment Type | transcription profiling by array |
| Study Type | WT vs. Mutant | Source | ArrayExpress |
| Curation Date | 2017-09-27 |
| description | We previously showed that nucleoredoxin (NRX) suppresses Wnt/beta-catenin signaling through its binding to Dishevelled (Dvl) (Nat Cell Biol 8, 501-508 (2006)). To clarify the in vivo role of NRX in mammals, we here generate NRX gene-knockout mice (NRX-/- mice) by homologous recombination. NRX-/- mice die around birth. Therefore, we performed microarray analyses with NRX+/+ and NRX-/- embryos of E9.5 and E11.5 stages. Surprisingly, in the genes commonly upregulated at both stages, we could not observe Wnt/beta-catenin targets. Rather, several target genes for Wnt/beta-catenin pathway, such as Frizzled2 and Occludin, are downregulated in NRX-/- whole embryos. Frizzled2 is a gene reportedly expressed in developmental heart. Indeed, by RT-PCR analyses we confirmed that the expression of Frizzled2, as well as other Wnt/beta-catenin target genes, was downregulated in embryonic heart of NRX-/- mice. We also found that the amount of unphosphorylated (i.e. activated) form of beta-catenin was downregulated in NRX-/- embryonic heart. These results reveal that NRX plays another role which was unidentified in culture cell studies; it is required for the maintenance of Wnt/beta-catenin signaling activity. Total RNAs were extracted from E9.5 and E11.5 embryos derived from NRX+/+ and NRX-/- C57BL/6J mice using RNeasy extraction kit (Qiagen). Two dye-swapped experiments were performed by hybridizing complimentary RNA (cRNA) labeled with either Cyanine (Cy) -3 or Cy-5 (Perkin-Elmer) onto Whole Mouse Genome Oligo Microarray (G4122A; Agilent Technologies). The signature genes with mean fold changes > +2.0 or < -2.0 at both stages were subjected for further evaluation. |
