title: Dullard/Ctdnep1 modulates WNT signalling activity for the formation of primordial germ cells in the mouse embryo.
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.
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors.forename: Satomi S
authors.initials: SS
authors.lastname: Tanaka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakane
authors.forename: Yasuka L
authors.initials: YL
authors.lastname: Yamaguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terabayashi
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakao
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Steiner
authors.forename: Patrick P L
authors.initials: PP
authors.lastname: Tam
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics; D000072261:Dishevelled Proteins; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D060508:Wnt3 Protein / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; D010750:Phosphoproteins; D051785:Smad Proteins; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D051176:beta Catenin; C581756:Dullard protein, mouse; D010749:Phosphoprotein Phosphatases