RESUMO
In all sexually reproducing organisms, cells of the germ line must transition from mitosis to meiosis. In mice, retinoic acid (RA), the extrinsic signal for meiotic initiation, activates transcription of Stra8, which is required for meiotic DNA replication and the subsequent processes of meiotic prophase. Here we report that RA also activates transcription of Rec8, which encodes a component of the cohesin complex that accumulates during meiotic S phase, and which is essential for chromosome synapsis and segregation. This RA induction of Rec8 occurs in parallel with the induction of Stra8, and independently of Stra8 function, and it is conserved between the sexes. Further, RA induction of Rec8, like that of Stra8, requires the germ-cell-intrinsic competence factor Dazl. Our findings strengthen the importance of RA and Dazl in the meiotic transition, provide important details about the Stra8 pathway, and open avenues to investigate early meiosis through analysis of Rec8 induction and function.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Meiose/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Proteínas de Ligação a RNA/genética , Tretinoína/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas de Ciclo Celular , Replicação do DNA/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Células Germinativas/crescimento & desenvolvimento , Masculino , Camundongos , Mitose/genética , Proteínas Nucleares/biossíntese , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Fosfoproteínas/biossíntese , Proteínas de Ligação a RNA/biossíntese , Transdução de Sinais/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Transcrição Gênica/efeitos dos fármacos , Tretinoína/administração & dosagemRESUMO
The transition from mitosis to meiosis is a defining juncture in the life cycle of sexually reproducing organisms. In yeast, the decision to enter meiosis is made before the single round of DNA replication that precedes the two meiotic divisions. We present genetic evidence of an analogous decision point in the germ line of a multicellular organism. The mouse Stra8 gene is expressed in germ cells of embryonic ovaries, where meiosis is initiated, but not in those of embryonic testes, where meiosis does not begin until after birth. Here we report that in female embryos lacking Stra8 gene function, the early, mitotic development of germ cells is normal, but these cells then fail to undergo premeiotic DNA replication, meiotic chromosome condensation, cohesion, synapsis and recombination. Combined with previous findings, these genetic data suggest that active differentiation of ovarian germ cells commences at a regulatory point upstream of premeiotic DNA replication.
Assuntos
Replicação do DNA , Meiose/genética , Ovário/embriologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oogênese/genética , Ovário/metabolismo , Proteínas/genética , Proteínas/metabolismo , Testículo/embriologia , Testículo/metabolismoRESUMO
Sex differences abound in human health and disease, as they do in other mammals used as models. The extent to which sex differences are conserved at the molecular level across species and tissues is unknown. We surveyed sex differences in gene expression in human, macaque, mouse, rat, and dog, across 12 tissues. In each tissue, we identified hundreds of genes with conserved sex-biased expression-findings that, combined with genomic analyses of human height, explain ~12% of the difference in height between females and males. We surmise that conserved sex biases in expression of genes otherwise operating equivalently in females and males contribute to sex differences in traits. However, most sex-biased expression arose during the mammalian radiation, which suggests that careful attention to interspecies divergence is needed when modeling human sex differences.