SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors
SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors
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DOI：
10.1016/j.ydbio.2004.07.011
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发表时间：
2004-10-15
影响因子：
2.7
通讯作者：
Lovell-Badge, R
中科院分区：
文献类型：
--
作者：
Sekido, R;Bar, I;Lovell-Badge, R
Y染色体基因Sry编码启动睾丸发育所需的转录因子。相关的常染色体基因 Sox9 在 Sry 转录开始后不久就会上调，并且被认为对于支持细胞的分化至关重要。产生支持细胞的谱系起源于生殖脊的体腔上皮 (CE)，但也来自能够产生间质细胞类型的细胞。目前尚不清楚 SRY 在这一谱系的衍生过程中发挥作用，也不知道这两个基因如何相互作用。为了研究表达 Sry 的细胞的身份，我们设计了两种由 Sry 启动子驱动的转基因：一种表达稳定的报告基因、人胎盘碱性磷酸酶 (hPLAP)，而第二种表达功能性 Myc 表位标记的 SRY 蛋白 (SRYMYC)。利用报告基因转录停止后持续的 hPLAP 活性，我们可以证明 Sry(hPLAP) 只在所有注定成为支持细胞的细胞中表达。 SRYMYC-单阳性细胞首先在性腺中观察到，而不是在 CE 中观察到。随后，它们变成了 SRYMYC/SOX9 双阳性细胞，但只持续了几个小时，然后才变成 SOX9 单阳性细胞。体腔上皮细胞迁移到性腺后，首先决定成为间质细胞或支持细胞，然后后者中SRY的瞬时表达通过上调Sox9决定其作为支持细胞的命运。 (C) 2004 Elsevier Inc. 保留所有权利。
The Y chromosome gene Sry encodes a transcription factor required to initiate testis development. The related autosomal gene Sox9 is upregulated shortly after the onset of Sry transcription and is thought essential for the differentiation of Sertoli cells. The lineage that gives rise to Sertoli cells has its origins within the coelomic epithelium (CE) of the genital ridge, but from cells also able to give rise to an interstitial cell type. It was not known at what point SRY acts in the derivation of this lineage or how the two genes interact. To investigate the identity of the cells expressing Sry, we designed two transgenes driven by the Sry promoter: one gives expression of a stable reporter, human placental alkaline phosphatase (hPLAP), while the second gives expression of a functional Myc-epitope tagged SRY protein (SRYMYC). Taking advantage of lasting hPLAP activity after transcription of the reporter gene has ceased, we could show that Sry(hPLAP) was expressed exclusively in all cells fated to become Sertoli cells. SRYMYC-single-positive cells were first observed in the gonad and not in the CE. Subsequently, they became SRYMYC/SOX9-double-positive, but only for a few hours before turning into SOX9-single-positive cells. After the coelomic epithelial cells migrate into the gonad, there is first a decision to become interstitial or supporting cells, and then the transient expression of SRY in the latter determines their fate as Sertoli cells by up-regulating Sox9. (C) 2004 Elsevier Inc. All rights reserved.