Y染色體基因Sry的表達(dá)決定了胚胎中早期性腺向睪丸發(fā)育，從而進(jìn)一步?jīng)Q定了個(gè)體的性別及其生殖細(xì)胞的類型,。但是對Sry基因的表達(dá)調(diào)控,，我們還知之甚少。來自日本的研究人員發(fā)現(xiàn)Six基因家族中的Six1和Six4在性別決定以及性腺發(fā)育中起了非常重要的作用,。同時(shí)敲除Six1和Six4的XY型小鼠胚胎會從雄性向雌性轉(zhuǎn)變,，并且Sry基因不能激活，在單獨(dú)敲除Six1或Six4的小鼠中則不會出現(xiàn)這種表型,。而在雙突變體XY型小鼠胚胎中外源表達(dá)Sry基因則會恢復(fù)雄性性狀,。并且無論是雄性還是雌性小鼠胚胎同時(shí)缺少Six1和Six4，會導(dǎo)致性腺前體細(xì)胞數(shù)量減少,，并最終導(dǎo)致性腺體積減小,。研究人員還找到了Six1/Six4在性腺發(fā)育過程中的兩個(gè)重要的下游信號通路：在雄性性別決定過程中，Six1/Six4通過調(diào)節(jié)Fog2（Zfpm2）從而誘導(dǎo)Sry的表達(dá),；在性腺前體細(xì)胞形成過程中,，Six1/Six4調(diào)節(jié)Nr5a1（Ad4BP/Sf1）的表達(dá)，從而影響性腺的大小,。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
