Y染色体基因Sry的表达决定了胚胎中早期性腺向睾丸发育，从而进一步决定了个体的性别及其生殖细胞的类型。但是对Sry基因的表达调控，我们还知之甚少。来自日本的研究人员发现Six基因家族中的Six1和Six4在性别决定以及性腺发育中起了非常重要的作用。同时敲除Six1和Six4的XY型小鼠胚胎会从雄性向雌性转变，并且Sry基因不能激活，在单独敲除Six1或Six4的小鼠中则不会出现这种表型。而在双突变体XY型小鼠胚胎中外源表达Sry基因则会恢复雄性性状。并且无论是雄性还是雌性小鼠胚胎同时缺少Six1和Six4，会导致性腺前体细胞数量减少，并最终导致性腺体积减小。研究人员还找到了Six1/Six4在性腺发育过程中的两个重要的下游信号通路：在雄性性别决定过程中，Six1/Six4通过调节Fog2（Zfpm2）从而诱导Sry的表达；在性腺前体细胞形成过程中，Six1/Six4调节Nr5a1（Ad4BP/Sf1）的表达，从而影响性腺的大小。（生物谷Bioon.com）
生物谷推荐英文摘要：
Developmental Cell DOI:10.1016/j.devcel.2013.06.018
Homeoproteins Six1 and Six4 Regulate Male Sex Determination and Mouse Gonadal Development
Yuka Fujimoto,1 Satomi S. Tanaka,1,* Yasuka L. Yamaguchi,1 Hiroki Kobayashi,1 Shunsuke Kuroki,2 Makoto Tachibana,2 Mai Shinomura,3 Yoshiakira Kanai,3 Ken-ichirou Morohashi,4 Kiyoshi Kawakami,5 and Ryuichi Nishinakamura1,*
The Y-linked gene Sry regulates mammalian sex determination in bipotential embryonic gonads. Here, we report that the transcription factors Six1 and Six4 are required for male gonadal differentiation. Loss of Six1 and Six4 together, but neither alone, resulted in a male-to-female sex-reversal phenotype in XY mutant gonads accompanied by a failure in Sry activation. Decreased gonadal precursor cell formation at the onset of Sry expression and a gonadal size reduction in both sexes were also found in mutant embryos. Forced Sry transgene expression in XY mutant gonads rescued testicular development but not the initial disruption to precursor growth. Furthermore, we identified two downstream targets of Six1/Six4 in gonadal development, Fog2 (Zfpm2) and Nr5a1 (Ad4BP/Sf1). These two distinct Six1/Six4-regulated pathways are considered to be crucial for gonadal development. The regulation of Fog2 induces Sry expression in male sex determination, and the regulation of Nr5a1 in gonadal precursor formation determines gonadal size.
