A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants

Shinya Aramaki, Katsuhiko Hayashi, Kazuki Kurimoto, Hiroshi Ohta, Yukihiro Yabuta, Hiroko Iwanari, Yasuhiro Mochizuki, Takao Hamakubo, Yuki Kato, Katsuhiko Shirahige, Mitinori Saitou

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126 Citations (Scopus)

Abstract

Germ cells ensure reproduction and heredity. In mice, primordial germ cells (PGCs), the precursors for spermatozoa and oocytes, are induced in pluripotent epiblast by BMP4 and WNT3, yet the underlying mechanism remains unclear. Here, using an invitro PGC specification system, we show that WNT3 induces many transcription factors associated withmesoderm in epiblast-like cells through β-CATENIN. Among these, T (BRACHYURY), a classical and conserved mesodermal factor, was essential for robust activation of Blimp1 and Prdm14, two of the germline determinants. T, but not SMAD1 or TCF1, binds distinct regulatory elements of both Blimp1 and Prdm14 and directly upregulates these genes, delineating the downstream PGC program. Without BMP4, a program induced by WNT3 prevents T from activating Blimp1 and Prdm14, demonstrating a permissive role of BMP4 in PGC specification. These findings establish the key signaling mechanism for, and a fundamental role of a mesodermal factor in, mammalian PGC specification.

Original languageEnglish
Pages (from-to)516-529
Number of pages14
JournalDevelopmental Cell
Volume27
Issue number5
DOIs
Publication statusPublished - Dec 9 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Aramaki, S., Hayashi, K., Kurimoto, K., Ohta, H., Yabuta, Y., Iwanari, H., Mochizuki, Y., Hamakubo, T., Kato, Y., Shirahige, K., & Saitou, M. (2013). A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants. Developmental Cell, 27(5), 516-529. https://doi.org/10.1016/j.devcel.2013.11.001