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OTX2 restricts entry to the mouse germline

Author

Listed:
  • Jingchao Zhang

    (School of Biological Sciences, University of Edinburgh)

  • Man Zhang

    (School of Biological Sciences, University of Edinburgh)

  • Dario Acampora

    (Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”)

  • Matúš Vojtek

    (School of Biological Sciences, University of Edinburgh)

  • Detian Yuan

    (Shandong University School of Medicine)

  • Antonio Simeone

    (Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”)

  • Ian Chambers

    (School of Biological Sciences, University of Edinburgh)

Abstract

The successful segregation of germ cells from somatic lineages is vital for sexual reproduction and species survival. In the mouse, primordial germ cells (PGCs), precursors of all germ cells, are induced from the post-implantation epiblast1. Induction requires BMP4 signalling to prospective PGCs2 and the intrinsic action of PGC transcription factors3–6. However, the molecular mechanisms that connect BMP4 to induction of the PGC transcription factors that are responsible for segregating PGCs from somatic lineages are unknown. Here we show that the transcription factor OTX2 is a key regulator of these processes. Downregulation of Otx2 precedes the initiation of the PGC programme both in vitro and in vivo. Deletion of Otx2 in vitro markedly increases the efficiency of PGC-like cell differentiation and prolongs the period of PGC competence. In the absence of Otx2 activity, differentiation of PGC-like cells becomes independent of the otherwise essential cytokine signals, with germline entry initiating even in the absence of the PGC transcription factor BLIMP1. Deletion of Otx2 in vivo increases PGC numbers. These data demonstrate that OTX2 functions repressively upstream of PGC transcription factors, acting as a roadblock to limit entry of epiblast cells to the germline to a small window in space and time, thereby ensuring correct numerical segregation of germline cells from the soma.

Suggested Citation

  • Jingchao Zhang & Man Zhang & Dario Acampora & Matúš Vojtek & Detian Yuan & Antonio Simeone & Ian Chambers, 2018. "OTX2 restricts entry to the mouse germline," Nature, Nature, vol. 562(7728), pages 595-599, October.
  • Handle: RePEc:nat:nature:v:562:y:2018:i:7728:d:10.1038_s41586-018-0581-5
    DOI: 10.1038/s41586-018-0581-5
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    Cited by:

    1. Sivakamasundari Vijayakumar & Roberta Sala & Gugene Kang & Angela Chen & Michelle Ann Pablo & Abidemi Ismail Adebayo & Andrea Cipriano & Jonas L. Fowler & Danielle L. Gomes & Lay Teng Ang & Kyle M. Lo, 2023. "Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Paraskevi Athanasouli & Martina Balli & Anchel Jaime-Soguero & Annekatrien Boel & Sofia Papanikolaou & Bernard K. Veer & Adrian Janiszewski & Tijs Vanhessche & Annick Francis & Youssef El Laithy & Ant, 2023. "The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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