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Publication : Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary.

First Author  Naillat F Year  2015
Journal  Exp Cell Res Volume  332
Issue  2 Pages  163-78
PubMed ID  25645944 Mgi Jnum  J:219786
Mgi Id  MGI:5629754 Doi  10.1016/j.yexcr.2015.01.010
Citation  Naillat F, et al. (2015) Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary. Exp Cell Res 332(2):163-78
abstractText  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.
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