OTX2 restricts entry to the mouse germline

Jingchao Zhang, Man Zhang (), Dario Acampora, Matúš Vojtek, Detian Yuan, Antonio Simeone and Ian Chambers ()
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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

Nature, 2018, vol. 562, issue 7728, 595-599

Abstract: 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.

Keywords: PGC-like Cells (PGCLC); Primordial Germ Cells (PGC); Transcription Factors Otx2; Epiblast Cells; EpiLCs (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (2)

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DOI: 10.1038/s41586-018-0581-5

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