title: Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary.
abstract: The indifferent mammalian embryonic gonad generates an ovary or testis, but the factors involved are still poorly known. The Wnt-4 signal represents one critical female determinant, since its absence leads to partial female-to-male sex reversal in mouse, but its signalling is as well implicated in the testis development. We used the Wnt-4 deficient mouse as a model to identify candidate gonadogenesis genes, and found that the Notum, Phlda2, Runx-1 and Msx1 genes are typical of the wild-type ovary and the Osr2, Dach2, Pitx2 and Tacr3 genes of the testis. Strikingly, the expression of these latter genes becomes reversed in the Wnt-4 knock-out ovary, suggesting a role in ovarian development. We identified the transcription factor Runx-1 as a Wnt-4 signalling target gene, since it is expressed in the ovary and is reduced upon Wnt-4 knock-out. Consistent with this, introduction of the Wnt-4 signal into early ovary cells ex vivo induces Runx-1 expression, while conversely Wnt-4 expression is down-regulated in the absence of Runx-1. We conclude that the Runx-1 gene can be a Wnt-4 signalling target, and that Runx-1 and Wnt-4 are mutually interdependent in their expression. The changes in gene expression due to the absence of Wnt-4 in gonads reflect the sexually dimorphic role of this signal and its complex gene network in mammalian gonad development.
authors: Academy of Finland, Centre of Excellence of Cell-Extracellular Matrix Research, Biocenter Oulu & Infotech Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland.
authors: Florence
authors: F
authors: Naillat
authors: Center for Systems Biology, Soochow University, Suzhou, China.
authors: Wenying
authors: W
authors: Yan
authors: Institute for Molecular Medicine, Helsinki, Finland.
authors: Riikka
authors: R
authors: Karjalainen
authors: Institute for Stem Cell Research, King׳s Buildings West, University of Edinburgh, UK.
authors: Anna
authors: A
authors: Liakhovitskaia
authors: Academy of Finland, Centre of Excellence of Cell-Extracellular Matrix Research, Biocenter Oulu & Infotech Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland.
authors: Anatoly
authors: A
authors: Samoylenko
authors: Academy of Finland, Centre of Excellence of Cell-Extracellular Matrix Research, Biocenter Oulu & Infotech Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland.
authors: Qi
authors: Q
authors: Xu
authors: Center for Systems Biology, Soochow University, Suzhou, China.
authors: Zhandong
authors: Z
authors: Sun
authors: Center for Systems Biology, Soochow University, Suzhou, China.
authors: Bairong
authors: B
authors: Shen
authors: Institute for Stem Cell Research, King׳s Buildings West, University of Edinburgh, UK.
authors: Alexander
authors: A
authors: Medvinsky
authors: Feinberg Cardiovascular Research Institute, Division of Medicine-Nephrology, Chicago, USA.
authors: Susan
authors: S
authors: Quaggin
authors: Academy of Finland, Centre of Excellence of Cell-Extracellular Matrix Research, Biocenter Oulu & Infotech Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland. Electronic address: seppo.vainio@oulu.fi.
authors: Seppo J
authors: SJ
authors: Vainio
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D008297:Male; D018345:Mice, Knockout; D010053:Ovary / Q000196:embryology / Q000378:metabolism*; D019849:Sex Determination Processes / Q000235:genetics; D046509:Tissue Culture Techniques; D060449:Wnt Signaling Pathway; D060528:Wnt4 Protein / Q000502:physiology*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse
keywords: Female development; Germ line; Organogenesis; Ovary; Runx-1; Sex determination; Somatic cells; Testis; Wnt-4