Divergent expression regulation of gonad development genes in medaka shows incomplete conservation of the downstream regulatory network of vertebrate sex determination.

Divergent expression regulation of gonad development genes in medaka shows incomplete conservation of the downstream regulatory network of vertebrate sex determination.
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DOI:
10.1093/molbev/mst130
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发表时间:
2013-10
影响因子:
10.7
通讯作者:
Schartl M
Schartl M
中科院分区:
生物学1区
文献类型:
--
作者:
Herpin A;Adolfi MC;Nicol B;Hinzmann M;Schmidt C;Klughammer J;Engel M;Tanaka M;Guiguen Y;Schartl M

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雄性或雌性性腺发育的遗传控制在不同的生物群体之间显示出位于遗传层次顶部的“主要性别决定基因”的显着多样性,而令人惊讶的是下游成分在进化上似乎更加保守。无需进一步研究,序列守恒就等同于功能守恒。我们使用青鳉鱼来研究这个范式的普遍性。在青鳉中,主要的雄性性别决定基因是 dmrt1bY,它是脊椎动物性别决定的高度保守的下游调节因子。为了了解其在编排复杂基因调控网络中的功能,我们确定了 Dmrt1bY 的靶基因和调控途径。通过转基因荧光报告鱼系、体内组织染色质免疫沉淀和体外基因调控测定来监测基因表达和相互作用,揭示了哺乳动物和青鳉之间的一致性,但也存在重大差异,特别是在典型的 Hedgehog 和 R-spondin/Wnt/Follistatin 信号通路的空间、时间表达模式和调控方面。对青鳉卵巢中 Foxl2 蛋白分布的检查确定了一个新的卵泡膜细胞亚群,其中卵巢型芳香酶转录调节似乎独立于 Foxl2。总之,这些数据表明,性别决定下游调控网络的调控不如之前想象的那么保守。
Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of “master sex-determining genes” at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.
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