REST and its downstream molecule Mek5 regulate survival of primordial germ cells

Daiji Okamura, Kentaro Mochizuki, Hirofumi Taniguchi, Yuko Tokitake, Makiko Ikeda, Yasuhiro Yamada, Cathy Tournier, Shinpei Yamaguchi, Takashi Tada, Hans R. Schöler, Yasuhisa Matsui

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

In mouse embryos, some primordial germ cells (PGCs) are eliminated by apoptosis, but the molecular pathways that lead to PGC survival versus apoptosis have not been fully characterized. Here, we found that REST (repressor element 1-silencing transcription factor), a transcription factor that binds a conserved regulatory element, NRSE/RE1, played a role in PGC survival. REST expression was higher in PGCs than in surrounding somatic cells. Moreover, in mouse embryos with a PGC-specific conditional REST mutation, the PGC population experienced more apoptosis and was significantly smaller than that in control embryos; these findings indicated that REST functioned in a cell-autonomous fashion that was critical for PGC survival. Several anti-apoptotic genes were among the previously identified REST-target gene candidates; moreover, some of these genes were downregulated in the REST-deficient PGCs. Mek5, which encodes a component in the a MAP kinase cascade, was one of these downregulated REST-target gene candidates, and a Mek5 mutation, like the REST mutation, caused an increase in PGC apoptosis; these finding suggested that REST promoted PGC survival via regulation of the Mek5 expression. Importantly, there were a normal number of PGCs in the REST mutants at birth, and both the male and female REST-mutant adults were fertile; these final observations revealed that the PGC population was very robust and could recover from a genetically induced reduction in cell number.

Original languageEnglish
Pages (from-to)190-202
Number of pages13
JournalDevelopmental Biology
Volume372
Issue number2
DOIs
Publication statusPublished - 2012 Dec 15

Keywords

  • Apoptosis
  • Knockout mouse
  • Mek5
  • Primordial germ cells
  • REST

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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