1] Laboratory of Bioresources, National Institute for Basic Biology, Okazaki 444-8585, Japan [2] Department of Basic Biology, the Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8585, Japan.
Center for Bioscience Research and Education, Utsunomiya University, Utsunomiya, Tochigi 321-8505, Japan.
Nat Commun. 2014 Jun 20;5:4157. doi: 10.1038/ncomms5157.
Sex chromosomes harbour a primary sex-determining signal that triggers sexual development of the organism. However, diverse sex chromosome systems have been evolved in vertebrates. Here we use positional cloning to identify the sex-determining locus of a medaka-related fish, Oryzias dancena, and find that the locus on the Y chromosome contains a cis-regulatory element that upregulates neighbouring Sox3 expression in developing gonad. Sex-reversed phenotypes in Sox3(Y) transgenic fish, and Sox3(Y) loss-of-function mutants all point to its critical role in sex determination. Furthermore, we demonstrate that Sox3 initiates testicular differentiation by upregulating expression of downstream Gsdf, which is highly conserved in fish sex differentiation pathways. Our results not only provide strong evidence for the independent recruitment of Sox3 to male determination in distantly related vertebrates, but also provide direct evidence that a novel sex determination pathway has evolved through co-option of a transcriptional regulator potentially interacted with a conserved downstream component.
性染色体包含一个主要的性别决定信号，触发生物体的性发育。然而，脊椎动物已经进化出了多种性染色体系统。在这里，我们使用定位克隆来鉴定一种与日本青鳉相关的鱼类，Oryzias dancena 的性别决定基因座，并发现 Y 染色体上的基因座包含一个顺式调控元件，该元件在发育中的性腺中上调邻近 Sox3 的表达。Sox3(Y) 转基因鱼的性反转表型和 Sox3(Y) 功能缺失突变体都表明其在性别决定中具有关键作用。此外，我们证明 Sox3 通过上调下游 Gsdf 的表达来启动睾丸分化，Gsdf 在鱼类性别分化途径中高度保守。我们的研究结果不仅为 Sox3 在亲缘关系较远的脊椎动物中被独立招募到雄性决定提供了强有力的证据，还为通过共同利用一个可能与保守下游成分相互作用的转录调节因子来进化新的性别决定途径提供了直接证据。
