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PMID:23469192

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Citation

Tanaka, SS, Nakane, A, Yamaguchi, YL, Terabayashi, T, Abe, T, Nakao, K, Asashima, M, Steiner, KA, Tam, PP and Nishinakamura, R (2013) Dullard/Ctdnep1 modulates WNT signalling activity for the formation of primordial germ cells in the mouse embryo. PLoS ONE 8:e57428

Abstract

Dullard/Ctdnep1 is a member of the serine/threonine phosphatase family of the C-terminal domain of eukaryotic RNA polymerase II. Embryos lacking Dullard activity fail to form primordial germ cells (PGCs). In the mouse, the formation of PGCs is influenced by BMP4 and WNT3 activity. Although Dullard is reputed to negatively regulate BMP receptor function, in this study we found mutations in Dullard had no detectable effect on BMP4 and p-Smad activity. Furthermore Dullard mutations did not influence the dosage-dependent inductive effect of Bmp4 in PGC formation. However, Dullard may function as a positive regulator of WNT signalling. Combined loss of one copy each of Dullard and Wnt3 had a synergistic effect on the reduction of PGC numbers in the compound heterozygous embryo. In addition, loss of Dullard function was accompanied by down-regulation of WNT/β-catenin signalling activity and a reduction in the level of Dishevelled 2 (Dvl2). Therefore, Dullard may play a role in the fine-tuning of WNT signalling activity by modulating the expression of ligands/antagonists and the availability of Dvl2 protein during specification of the germ cell lineage.

Links

PubMed PMC3587611 Online version:10.1371/journal.pone.0057428

Keywords

Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Bone Morphogenetic Protein 4/genetics; Bone Morphogenetic Protein 4/metabolism; Cell Lineage/genetics; Embryo, Mammalian; Gene Expression Regulation, Developmental; Germ Cells/cytology; Germ Cells/metabolism; Heterozygote; Homozygote; Mice; Morphogenesis/genetics; Mutation; Phosphoprotein Phosphatases/deficiency; Phosphoprotein Phosphatases/genetics; Phosphoproteins/genetics; Phosphoproteins/metabolism; Signal Transduction/genetics; Smad Proteins/genetics; Smad Proteins/metabolism; Wnt3 Protein/genetics; Wnt3 Protein/metabolism; beta Catenin/genetics; beta Catenin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CNEP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q60838

F

Seeded From UniProt

complete

MOUSE:CNEP1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CNEP1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CNEP1

acts_upstream_of_or_within

GO:0007498: mesoderm development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5510826

P

  • results_in_development_of:(EMAPA:31862)

Seeded From UniProt

complete

MOUSE:CNEP1

acts_upstream_of_or_within

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5510826

P

  • regulates_o_occurs_in:(EMAPA:16087)

Seeded From UniProt

complete

MOUSE:DVL2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q3TP92

F

Seeded From UniProt

complete

MOUSE:CNEP1

acts_upstream_of_or_within

GO:0007498: mesoderm development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5510826

P

results_in_development_of:(EMAPA:31862)

Seeded From UniProt

complete

MOUSE:CNEP1

acts_upstream_of_or_within

GO:0007276: gamete generation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98955

P

Seeded From UniProt

complete

MOUSE:CNEP1

acts_upstream_of_or_within

GO:0007276: gamete generation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5510826

P

Seeded From UniProt

complete

MOUSE:CNEP1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CNEP1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CNEP1

acts_upstream_of_or_within

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5510826

P

regulates_o_occurs_in:(EMAPA:16087)

Seeded From UniProt

complete

MOUSE:WNT3

acts_upstream_of_or_within

GO:0007276: gamete generation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1914431

P

Seeded From UniProt

complete

Notes

See also

References

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