Kent J, Wheatley S C, Andrews J E, Sinclair A H, Koopman P
Centre for Molecular and Cellular Biology, The University of Queensland, Brisbane, Australia.
Development. 1996 Sep;122(9):2813-22. doi: 10.1242/dev.122.9.2813.
Mutation analyses of patients with campomelic dysplasia, a bone dysmorphology and XY sex reversal syndrome, indicate that the SRY-related gene SOX9 is involved in both skeletal development and sex determination. To clarify the role SOX9 plays in vertebrate sex determination, we have investigated its expression during gonad development in mouse and chicken embryos. In the mouse, high levels of Sox9 mRNA were found in male (XY) but not female (XX) genital ridges, and were localised to the sex cords of the developing testis. Purified fetal germ cells lacked Sox9 expression, indicating that Sox9 expression is specific to the Sertoli cell lineage. Sex specificity of SOX9 protein expression was confirmed using a polyclonal antiserum. The timing and cell-type specificity of Sox9 expression suggests that Sox9 may be directly regulated by SRY. Male-specific expression of cSOX9 mRNA during the sex determination period was also observed in chicken genital ridges. The conservation of sexually dimorphic expression in two vertebrate classes which have significant differences in their sex determination mechanisms, points to a fundamental role for SOX9 in testis determination in vertebrates. Sox9 expression was maintained in the mouse testis during fetal and adult life, but no expression was seen at any stage by in situ hybridisation in the developing ovary. Male-specific expression was also observed in the cells surrounding the Müllerian ducts and in the epididymis, and expression in both sexes was detected in the developing collecting ducts of the metanephric kidney. These results suggest that SOX9 may have a wider role in the development of the genitourinary system.
弯肢性发育不良是一种骨骼形态异常和XY性反转综合征，对该疾病患者的突变分析表明，与SRY相关的基因SOX9参与骨骼发育和性别决定过程。为阐明SOX9在脊椎动物性别决定中的作用，我们研究了其在小鼠和鸡胚胎性腺发育过程中的表达情况。在小鼠中，发现雄性（XY）而非雌性（XX）生殖嵴中有高水平的Sox9 mRNA，且定位于发育中睾丸的性索。纯化的胎儿生殖细胞缺乏Sox9表达，表明Sox9表达具有支持细胞谱系特异性。使用多克隆抗血清证实了SOX9蛋白表达的性别特异性。Sox9表达的时间和细胞类型特异性表明，Sox9可能受SRY直接调控。在鸡的生殖嵴中也观察到了性别决定期cSOX9 mRNA的雄性特异性表达。在性别决定机制存在显著差异的两类脊椎动物中，性二态性表达具有保守性，这表明SOX9在脊椎动物睾丸决定中起基本作用。在小鼠胎儿期和成年期睾丸中均维持Sox9表达，但在发育中的卵巢中，原位杂交在任何阶段均未检测到表达。在缪勒管周围细胞和附睾中也观察到雄性特异性表达，在两性中均检测到其在发育中的后肾集合管中的表达。这些结果表明，SOX9可能在泌尿生殖系统发育中发挥更广泛的作用。
