Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Dev Biol. 2012 Oct 1;370(1):24-32. doi: 10.1016/j.ydbio.2012.06.009. Epub 2012 Jun 15.
The bipotential gonad expresses genes associated with both the male and female pathways. Adoption of the male testicular fate is associated with the repression of many female genes including Wnt4. However, the importance of repression of Wnt4 to the establishment of male development was not previously determined. Deletion of either Fgf9 or Fgfr2 in an XY gonad resulted in up-regulation of Wnt4 and male-to-female sex reversal. We investigated whether the deletion if Wnt4 could rescue sex reversal in Fgf9 and Fgfr2 mutants. XY Fgf9/Wnt4 and Fgfr2/Wnt4 double mutants developed testes with male somatic and germ cells present, suggesting that the primary role of Fgf signaling is the repression of female-promoting genes. Thus, the decision to adopt the male fate is based not only on whether male genes, such as Sox9, are expressed, but also on the active repression of female genes, such as Wnt4. Because loss of Wnt4 results in the up-regulation of Fgf9, we also tested the possibility that derepression of Fgf9 was responsible for the aspects of male development observed in XX Wnt4 mutants. However, we found that the relationship between these two signaling factors is not symmetric: loss of Fgf9 in XX Wnt4(-/-) gonads does not rescue their partial female-to-male sex-reversal.
双潜能性腺表达与男性和女性途径相关的基因。雄性睾丸命运的采用与许多女性基因的抑制有关，包括 Wnt4。然而，Wnt4 的抑制对男性发育的建立的重要性以前没有确定。在 XY 性腺中删除 Fgf9 或 Fgfr2 会导致 Wnt4 的上调和雄性到雌性的性别反转。我们研究了删除 Wnt4 是否可以挽救 Fgf9 和 Fgfr2 突变体中的性别反转。XY Fgf9/Wnt4 和 Fgfr2/Wnt4 双突变体发育出具有雄性体和生殖细胞的睾丸，表明 Fgf 信号的主要作用是抑制雌性促进基因。因此，采用雄性命运的决定不仅取决于雄性基因（如 Sox9）是否表达，还取决于对雌性基因（如 Wnt4）的积极抑制。由于 Wnt4 的缺失导致 Fgf9 的上调，我们还测试了 Fgf9 去抑制是否是 XX Wnt4 突变体中观察到的雄性发育方面的原因。然而，我们发现这两个信号因子之间的关系不是对称的：在 XX Wnt4(-/-) 性腺中缺失 Fgf9 并不能挽救它们部分的雌性到雄性的性别反转。
