Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
27 07 2021
Historique:
entrez: 24 7 2021
pubmed: 25 7 2021
medline: 15 12 2021
Statut: ppublish

Résumé

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

Identifiants

pubmed: 34301885
pii: 2023376118
doi: 10.1073/pnas.2023376118
pmc: PMC8325354
pii:
doi:

Substances chimiques

CTNNB1 protein, mouse 0
Octamer Transcription Factor-3 0
Pou5f1 protein, mouse 0
Wnt Proteins 0
beta Catenin 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Medical Research Council
ID : MC_U142684167
Pays : United Kingdom

Informations de copyright

Copyright © 2021 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

The authors declare no competing interest.

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Auteurs

Morgane Le Rolle (M)

CNRS, Inserm, Institut de Biologie Valrose, Université Côte d'Azur, Parc Valrose, 06108 Nice Cedex 2, France.

Filippo Massa (F)

CNRS, Inserm, Institut de Biologie Valrose, Université Côte d'Azur, Parc Valrose, 06108 Nice Cedex 2, France.
Inovarion, 75005 Paris, France.

Pam Siggers (P)

Mammalian Genetics Unit, Medical Research Council Harwell Institute, Oxfordshire OX11 0RD, United Kingdom.

Laurent Turchi (L)

CNRS, Inserm, Institut de Biologie Valrose, Université Côte d'Azur, Parc Valrose, 06108 Nice Cedex 2, France.
Délégation à la Recherche Clinique et à l'Innovation, Centre Hospitalier Universitaire de Nice, 06000 Nice, France.

Agnès Loubat (A)

CNRS, Inserm, Institut de Biologie Valrose, Université Côte d'Azur, Parc Valrose, 06108 Nice Cedex 2, France.

Bon-Kyoung Koo (BK)

Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, The Netherlands.
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, 1030 Vienna, Austria.

Hans Clevers (H)

Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, The Netherlands.

Andy Greenfield (A)

Mammalian Genetics Unit, Medical Research Council Harwell Institute, Oxfordshire OX11 0RD, United Kingdom.

Andreas Schedl (A)

CNRS, Inserm, Institut de Biologie Valrose, Université Côte d'Azur, Parc Valrose, 06108 Nice Cedex 2, France.

Marie-Christine Chaboissier (MC)

CNRS, Inserm, Institut de Biologie Valrose, Université Côte d'Azur, Parc Valrose, 06108 Nice Cedex 2, France.

Anne-Amandine Chassot (AA)

CNRS, Inserm, Institut de Biologie Valrose, Université Côte d'Azur, Parc Valrose, 06108 Nice Cedex 2, France; Amandine.CHASSOT@univ-cotedazur.fr.

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