Töhönen V, Osterlund C, Nordqvist K
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14208-13. doi: 10.1073/pnas.95.24.14208.
To isolate genes involved in morphogenic aspects of testis development, and which may act in cell signaling pathways downstream of the testis-determining gene Sry, we have developed a modified mRNA differential display method named signal peptide differential display. It was used to target those genes that encode proteins having a signal peptide sequence. By using this method, we isolated a gene named testatin. This gene was found to be related to a group of genes that encodes cysteine protease inhibitors known as cystatins. Cystatins and their target proteases have been associated with tumor formation and metastasis, but also are involved in natural tissue remodeling events such as bone resorption and embryo implantation. We show that testatin expression is restricted to fetal gonads and adult testis. Furthermore, testatin is expressed during testis cord formation in pre-Sertoli cells, believed to be the site of Sry action, at a time immediately after the peak of Sry expression. This finding suggests that testatin might be activated by transcription factors that are known to orchestrate the early testis development pathway. This gene therefore represents one of the putative downstream targets likely to have an essential role in tissue reorganization during early testis development.
为了分离参与睾丸发育形态发生方面的基因，这些基因可能在睾丸决定基因Sry下游的细胞信号通路中发挥作用，我们开发了一种改良的mRNA差异显示方法，称为信号肽差异显示。它用于靶向那些编码具有信号肽序列蛋白质的基因。通过使用这种方法，我们分离出了一个名为testatin的基因。发现该基因与一组编码称为胱抑素的半胱氨酸蛋白酶抑制剂的基因有关。胱抑素及其靶蛋白酶不仅与肿瘤形成和转移有关，还参与自然组织重塑事件，如骨吸收和胚胎植入。我们表明，testatin表达仅限于胎儿性腺和成年睾丸。此外，testatin在睾丸索形成过程中在前支持细胞中表达，前支持细胞被认为是Sry作用的部位，在Sry表达峰值之后的即刻。这一发现表明，testatin可能被已知协调早期睾丸发育途径的转录因子激活。因此，该基因代表了可能在早期睾丸发育过程中组织重组中起重要作用的假定下游靶点之一。
