Zhao Liang, Arsenault Michel, Ng Ee Ting, Longmuss Enya, Chau Tevin Chui-Ying, Hartwig Sunny, Koopman Peter
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island,550 University Avenue, Charlottetown, PE, Canada C1A 4P3.
Dev Biol. 2017 Mar 1;423(1):46-56. doi: 10.1016/j.ydbio.2017.01.013. Epub 2017 Jan 21.
The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation. Finally, our data reveal that SOX4 (and, to a lesser extent, SOX11 and -12) repressed transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads, raising the possibility that SOXC proteins may function as transcriptional repressors in a context-dependent manner.
C组SOX转录因子SOX4、-11和-12在多个器官的发育中发挥着重要且相互重叠的作用。在此，我们研究了SoxC基因在小鼠性腺发育过程中的作用。这三个基因在两性发育中的性腺中均有表达，主要在体细胞中表达，其中Sox4的表达最为强烈。Sox4基因缺失导致卵巢和睾丸均延长，睾丸索数量增加。虽然雌性生殖细胞正常进入减数分裂，但雄性生殖细胞中分化标记物Nanos2和Dnmt3l的水平降低，多能性基因Cripto和Nanog的水平升高，这表明SOX4通常可能起到限制雄性生殖细胞多能性时期并确保其正常分化的作用。最后，我们的数据表明，SOX4（以及在较小程度上的SOX11和-12）通过胎儿性腺中上游睾丸特异性增强子核心（TESCO）元件抑制性别决定基因Sox9的转录，这增加了SOXC蛋白可能以上下文依赖的方式作为转录抑制因子发挥作用的可能性。
