Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination
Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination
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DOI：
10.1016/j.ydbio.2005.08.039
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发表时间：
2005-11-01
影响因子：
2.7
通讯作者：
Koopman, P
中科院分区：
文献类型：
--
作者：
Wilhelm, D;Martinson, F;Koopman, P
我们制备了一种特异性识别内源性小鼠SRY蛋白的抗体，并利用该抗体研究了SRY在睾丸决定中的分子和细胞作用模式。我们发现SRY蛋白的表达密切反映了小鼠生殖嵴中Sry mRNA的表达，并且在mRNA停止检测后6至8小时可检测到。表达SRY的体细胞亚群几乎立即开始表达SOX 9。由于这些Sox 9阳性细胞逐渐发育为支持细胞，因此似乎SRY表达标志着前支持细胞谱系，并导致Sox 9表达细胞自主上调。然而，一小部分SOX 9阳性细胞似乎不表达SRY，这可能反映了旁分泌信号在这些细胞中激活Sox 9转录的额外参与。我们通过离体细胞混合实验证实，SRY能够参与受体介导的信号传导以上调Sox 9表达。最后，我们通过使用特异性抑制剂表明，致病信号分子是前列腺素D-2（PGD（2）），并且PGD 2可以诱导培养的XX性腺中Sox 9的转录。我们的数据表明了一种机制，即Sry使用细胞自主机制和PGD（2）介导的信号传导机制来刺激Sox 9的表达并诱导体内支持细胞的分化。(c)2005年爱思唯尔公司All rights reserved.
We have raised an antibody specifically recognizing endogenous mouse SRY protein and used it to investigate the molecular and cellular mode of action of SRY in testis determination. We find that expression of SRY protein closely mirrors the expression of Sry mRNA in Mouse genital ridges and is detectable for 6 to 8 h after the mRNA ceases to be detectable. The subset of somatic cells that expresses SRY begins to express SOX9 almost immediately. Since these SOX9-positive cells go oil to develop as Sertoli cells, it appears that SRY expression marks the pre-Sertoli cell lineage and leads to up-regulation of Sox9 expression cell-autonomously. However, a small proportion of SOX9-positive cells did not appear to express SRY, possibly reflecting the additional involvement of paracrine signaling in activating Sox9 transcription in these cells. We confirmed by ex vivo cell mixing experiments that SRY is able to engage receptor-mediated signaling to up-regulate Sox9 expression. Finally, we showed by employing specific inhibitors that the causative signaling molecule is prostaglandin D-2 (PGD(2)) and that PGD2 call induce Sox9 transcription in Cultured XX gonads. Our data indicate a mechanism whereby Sry; uses both a cell-autonomous mechanism and a PGD(2)-mediated signaling mechanism to stimulate expression of Sox9 and induce the differentiation of Sertoli cells in vivo. (c) 2005 Elsevier Inc. All rights reserved.