Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries
| العنوان: | Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries |
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| المؤلفون: | Morgane Le Rolle, Anne-Amandine Chassot, Pam Siggers, Filippo Massa, Marie-Christine Chaboissier, Bon-Kyoung Koo, Andreas Schedl, Hans Clevers, Agnès Loubat, Laurent Turchi, Andy Greenfield |
| المساهمون: | Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), MRC Harwell Institute [UK], Hubrecht Institute [Utrecht, Netherlands], University Medical Center [Utrecht]-Royal Netherlands Academy of Arts and Sciences (KNAW), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), ANR-20-CE14-0022,ARDIGERM,Acide rétinoïque dans la différenciation des cellules germinales et la méiose(2020), ANR-13-BSV2-0017,ARGONADS,Acide rétinoique et devenir des cellules germinales(2013), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Chaboissier, Marie-Christine, Acide rétinoïque dans la différenciation des cellules germinales et la méiose - - ARDIGERM2020 - ANR-20-CE14-0022 - AAPG2020 - VALID, Blanc 2013 - Acide rétinoique et devenir des cellules germinales - - ARGONADS2013 - ANR-13-BSV2-0017 - Blanc 2013 - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Hubrecht Institute for Developmental Biology and Stem Cell Research, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHASSOT, Anne Amandine |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2021, 118 (30), pp.e2023376118. ⟨10.1073/pnas.2023376118⟩ Proceedings of the National Academy of Sciences of the United States of America, 2021, 118 (30), pp.e2023376118. ⟨10.1073/pnas.2023376118⟩ Proceedings of the National Academy of Sciences of the United States of America, 118(30). National Academy of Sciences |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Pluripotent Stem Cells, germ cells, beta Catenin/genetics, Pluripotency & Differentiation, [SDV]Life Sciences [q-bio], Biology, Inbred C57BL, 03 medical and health sciences, Mice, 0302 clinical medicine, Meiosis, Primordial germ cell, medicine, Animals, Germ Cells/cytology, Wnt Proteins/genetics, Gametogenesis, beta Catenin, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Wnt signaling pathway, Cell Differentiation, Pluripotent Stem Cells/cytology, WNT/β-catenin, differentiation, Cell cycle, Biological Sciences, POU5F1/OCT4, Embryonic stem cell, Cell biology, Sexual reproduction, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Wnt Proteins, medicine.anatomical_structure, Female, ovary, Signal transduction, Octamer Transcription Factor-3, 030217 neurology & neurosurgery, Germ cell, Octamer Transcription Factor-3/genetics, Developmental Biology |
| الوصف: | Significance In the mammalian ovary, primordial germ cells maintain a genomic program associated with pluripotency until they stop proliferating, move toward oogenesis, and enter meiosis. The molecular mechanisms that enable primordial germ cells to exit pluripotency and enter meiosis in a timely manner are unclear, and their identification represents a major challenge in reproductive biology because the fertility of each individual depends on this. Evidence that cessation of germ cell proliferation is a cell-autonomous event, unrelated to the number of cell divisions, led to a search for an intrinsic timing mechanism that has long remained elusive. We describe here that WNT/β-catenin signaling regulates this timing and coordinates the transition from pluripotent to gametogenesis-competent germ cells. 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0027-8424 1091-6490 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::32b8b5f82de617033f1b5409e3c126ab https://hal.archives-ouvertes.fr/hal-03357217/document |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....32b8b5f82de617033f1b5409e3c126ab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00278424 10916490 |
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