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DOI10.1073/pnas.2023376118
Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries
Le Rolle M.; Massa F.; Siggers P.; Turchi L.; Loubat A.; Koo B.-K.; Clevers H.; Greenfield A.; Schedl A.; Chaboissier M.-C.; Chassot A.-A.
发表日期2021
ISSN0027-8424
卷号118期号:30
英文摘要Germ cells form the basis for sexual reproduction by producing gametes. In ovaries, primordial germ cells exit the cell cycle and the pluripotency-associated state, differentiate into oogonia, and initiate meiosis. Despite the importance of germ cell differentiation for sexual reproduction, signaling pathways regulating their fate remain largely unknown. Here, we show in mouse embryonic ovaries that germ cell–intrinsic β-catenin activity maintains pluripotency and that its repression is essential to allow differentiation and meiosis entry in a timely manner. Accordingly, in β-catenin loss-of-function and gain-of-function mouse models, the germ cells precociously enter meiosis or remain in the pluripotent state, respectively. We further show that interaction of β-catenin and the pluripotent-associated factor POU5F1 in the nucleus is associated with germ cell pluripotency. The exit of this complex from the nucleus correlates with germ cell differentiation, a process promoted by the up-regulation of Znrf3, a negative regulator of WNT/β-catenin signaling. Together, these data identify the molecular basis of the transition from primordial germ cells to oogonia and demonstrate that β-catenin is a central gatekeeper in ovarian differentiation and gametogenesis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Differentiation; Germ cells; Ovary; POU5F1/OCT4; WNT/β-catenin
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/238846
作者单位CNRS, Inserm, Institut de Biologie Valrose, Université Côte d’Azur, Parc Valrose, Nice Cedex 2, 06108, France; Inovarion, Paris, 75005, France; Mammalian Genetics Unit, Medical Research Council Harwell Institute, Oxfordshire, OX11 0RD, United Kingdom; Délégation à la Recherche Clinique et à l’Innovation, Centre Hospitalier Universitaire de Nice, Nice, 06000, France; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht, 3584 CT, Netherlands; Institute of Molecular Biotechnology, the Austrian Academy of Sciences, Vienna Biocenter, Vienna, 1030, Austria
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Le Rolle M.,Massa F.,Siggers P.,et al. Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries[J],2021,118(30).
APA Le Rolle M..,Massa F..,Siggers P..,Turchi L..,Loubat A..,...&Chassot A.-A..(2021).Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA Le Rolle M.,et al."Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).
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