Retinoic Acid Activates Two Pathways Required for Meiosis in Mice
The transition from mitosis to meiosis is a defining feature of germ cells, the precursors of eggs and sperm. In mice, retinoic acid (RA), a vitamin A derivative, induces expression of the gene Stra8, which in turn is required for the first critical steps of meiosis. The timing of Stra8 expression in mammalian germ cells is influenced by an RA-degrading enzyme, CYP26B1, that is normally expressed in fetal testes to delay meiosis in males. It is unknown if Stra8 is RA's only meiosis-inducing target in germ cells or if other such genes are regulated by RA independently of Stra8. To investigate this question, we generated two lines of mice: Cyp26b1 mutants and Stra8 mutants. Our genetic experiments comparing germ cell development in these two mutants revealed a new RA target, Rec8. We demonstrate that Rec8 upregulation by RA occurs in the same temporal and spatial manner as Stra8, but Rec8 expression is independent of Stra8. Rec8, like Stra8, plays a critical role during early meiotic processes, suggesting that RA induces meiosis in at least two independent pathways. These findings expand our understanding of the gene regulatory network involved in meiotic initiation in mammals.
Vyšlo v časopise:
Retinoic Acid Activates Two Pathways Required for Meiosis in Mice. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004541
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004541
Souhrn
The transition from mitosis to meiosis is a defining feature of germ cells, the precursors of eggs and sperm. In mice, retinoic acid (RA), a vitamin A derivative, induces expression of the gene Stra8, which in turn is required for the first critical steps of meiosis. The timing of Stra8 expression in mammalian germ cells is influenced by an RA-degrading enzyme, CYP26B1, that is normally expressed in fetal testes to delay meiosis in males. It is unknown if Stra8 is RA's only meiosis-inducing target in germ cells or if other such genes are regulated by RA independently of Stra8. To investigate this question, we generated two lines of mice: Cyp26b1 mutants and Stra8 mutants. Our genetic experiments comparing germ cell development in these two mutants revealed a new RA target, Rec8. We demonstrate that Rec8 upregulation by RA occurs in the same temporal and spatial manner as Stra8, but Rec8 expression is independent of Stra8. Rec8, like Stra8, plays a critical role during early meiotic processes, suggesting that RA induces meiosis in at least two independent pathways. These findings expand our understanding of the gene regulatory network involved in meiotic initiation in mammals.
Zdroje
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Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2014 Číslo 8
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