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Nucleoredoxin is required for the maintenance of Wnt/β-catenin signaling in mice embryo

ABSTRACT: We previously showed that nucleoredoxin (NRX) suppresses Wnt/β-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/β-catenin targets. Rather, several target genes for Wnt/β-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/β-catenin target genes, was downregulated in embryonic heart of NRX-/- mice. We also found that the amount of unphosphorylated (i.e. activated) form of β-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/β-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.

ORGANISM(S): Mus musculus  

SUBMITTER: Daisuke Okuzaki   Hiroshi Nojima  Yosuke Funato  Hiroaki Miki 

PROVIDER: E-GEOD-21954 | ArrayExpress | 2010-10-26



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Nucleoredoxin sustains Wnt/β-catenin signaling by retaining a pool of inactive dishevelled protein.

Funato Yosuke Y   Terabayashi Takeshi T   Sakamoto Reiko R   Okuzaki Daisuke D   Ichise Hirotake H   Nojima Hiroshi H   Yoshida Nobuaki N   Miki Hiroaki H  

Current biology : CB 20101021 21

Overexpression of Dishevelled (Dvl), an essential component of the Wnt signaling pathway, is frequently associated with tumors, and thus the Dvl protein level must be tightly controlled to sustain Wnt signaling without causing tumors. Kelch-like 12 (KLHL12) targets Dvl for ubiquitination and degradation, suggesting its potential importance in avoiding aberrant Dvl overexpression. However, the regulatory mechanism of the KLHL12 activity remained elusive. We show here that nucleoredoxin (NRX) dete  ...[more]

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