A critical time window of Sry action in gonadal sex determination in mice
A critical time window of Sry action in gonadal sex determination in mice
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DOI：
10.1242/dev.029587
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发表时间：
2009-01-01
期刊：
影响因子：
4.6
通讯作者：
Kanai, Yoshiakira
中科院分区：
文献类型：
--
作者：
Hiramatsu, Ryuji;Matoba, Shogo;Kanai, Yoshiakira
在哺乳动物中，Y连锁的性别决定基因Sry cell-自主地通过含有SRY-box基因9(Sox9)的SRY-box促进支持细胞从双潜能支持细胞前体分化为支持细胞，导致睾丸形成。在没有Sry作用的情况下，支持细胞分化为颗粒细胞，导致卵巢发育。然而，Sry如何在时空上将支持细胞从雌性途径切换到雄性途径还知之甚少。我们在Hsp70.3启动子的控制下建立了一种新型的转基因小鼠系，该品系含有可诱导的Sry转基因基因。对这些小鼠的分析表明，Sry诱导睾丸发育的能力被限制在大约11.0-11.25dpc，对应于Sry在XY性腺开始正常表达后6小时的时间窗口。如果Sry在11.3dpc后被激活，则Sox9的激活不会保持，从而导致卵巢发育。该时间窗口由参与支持细胞建立和脊髓组织所需的高-FGF9/低-WNT4信令状态的能力来界定。我们的结果表明，在最初的6小时阶段，Sry的作用对于FGF9/WNT4信号模式从雌性到雄性的切换是至关重要的。
In mammals, the Y-linked sex-determining gene Sry cell-autonomously promotes Sertoli cell differentiation from bipotential supporting cell precursors through SRY-box containing gene 9 (Sox9), leading to testis formation. Without Sry action, the supporting cells differentiate into granulosa cells, resulting in ovarian development. However, how Sry acts spatiotemporally to switch supporting cells from the female to the male pathway is poorly understood. We created a novel transgenic mouse line bearing an inducible Sry transgene under the control of the Hsp70.3 promoter. Analysis of these mice demonstrated that the ability of Sry to induce testis development is limited to approximately 11.0-11.25 dpc, corresponding to a time window of only 6 hours after the normal onset of Sry expression in XY gonads. If Sry was activated after 11.3 dpc, Sox9 activation was not maintained, resulting in ovarian development. This time window is delimited by the ability to engage the high-FGF9/low-WNT4 signaling states required for Sertoli cell establishment and cord organization. Our results indicate the overarching importance of Sry action in the initial 6-hour phase for the female-to-male switching of FGF9/WNT4 signaling patterns.