ZNRF3 functions in mammalian sex determination by inhibiting canonical WNT signaling

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ZNRF3 functions in mammalian sex determination by inhibiting canonical WNT signaling
 
Harris, Abigail; Siggers, Pam; Corrochano, Silvia; Warr, Nick; Sagar, Danielle; Grimes, Daniel T.; Suzuki, Makoto; Burdine, Rebecca D.; Cong, Feng; Koo, Bon Kyoung; Clevers, Hans; Stévant, Isabelle; Nef, Serge; Wells, Sara; Brauner, Raja; Rhouma, Bochra Ben; Belguith, Neïla; Eozenou, Caroline; Bignon-Topalovic, Joelle; Bashamboo, Anu; McElreavey, Ken; Greenfield, Andy
(2018) Proceedings of the National Academy of Sciences of the United States of America, volume 115, issue 21, pp. 5474 - 5479
(Article)
Abstract
Mammalian sex determination is controlled by the antagonistic interactions of two genetic pathways: The SRY-SOX9-FGF9 network promotes testis determination partly by opposing proovarian pathways, while RSPO1/WNT-β-catenin/FOXL2 signals control ovary development by inhibiting SRY-SOX9-FGF9. The molecular basis of this mutual antagonism is unclear. Here we show that ZNRF3, a WNT signaling ... read more
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Keywords: DSD, Organogenesis, Sex determination, WNT signaling, ZNRF3, General
DOI: https://doi.org/10.1073/pnas.1801223115
ISSN: 0027-8424
Publisher: National Academy of Sciences
Note: Funding Information: We thank the husbandry team in Ward 5 of the Mary Lyon Centre at Harwell and the Frozen Embryo and Sperm Archive (FESA) and histology teams. We thank Dagmar Wilhelm for the kind gift of anti-FOXL2 antibody. We thank Phil Johnson for zebrafish husbandry. We acknowledge European Cooperation in Science & Technology (COST) Action BM1303 (DSDnet). This work was supported by the Medical Research Council by core funding Grant MC_U142684167 (to A.G.) at the Harwell Institute, and the Agence Nationale de la Recherche Grant ANR-10-LABX-73 (to K.M.). S.N. acknowledges support from Swiss National Science Foundation Grant 31003A_173070. M.S. was a visiting scientist supported by the Strategic International Research Exchange Program between Princeton University and National Institutes of Natural Sciences, Japan. D.T.G. was supported by National Institute of Arthritis and Mucoskeletal and Skin Diseases Pathway to Independence Award 1K99AR070905. Work in the R.D.B. laboratory is supported by the National Institute of Child Health and Development Grant 2R01HD048584. Funding Information: ACKNOWLEDGMENTS. We thank the husbandry team in Ward 5 of the Mary Lyon Centre at Harwell and the Frozen Embryo and Sperm Archive (FESA) and histology teams. We thank Dagmar Wilhelm for the kind gift of anti-FOXL2 antibody. We thank Phil Johnson for zebrafish husbandry. We acknowledge European Cooperation in Science & Technology (COST) Action BM1303 (DSDnet). This work was supported by the Medical Research Council by core funding Grant MC_U142684167 (to A.G.) at the Harwell Institute, and the Agence Nationale de la Recherche Grant ANR-10-LABX-73 (to K.M.). S.N. acknowledges support from Swiss National Science Foundation Grant 31003A_173070. M.S. was a visiting scientist supported by the Strategic International Research Exchange Program between Princeton University and National Institutes of Natural Sciences, Japan. D.T.G. was supported by National Institute of Arthritis and Mucoskeletal and Skin Diseases Pathway to Independence Award 1K99AR070905. Work in the R.D.B. laboratory is supported by the National Institute of Child Health and Development Grant 2R01HD048584. Publisher Copyright: © 2018 National Academy of Sciences. All Rights Reserved.
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