アクティブボード・２０１１年　６月
　　　　　・・・・・２０１１年　６月　１日更新・・・・・

研究発表を行った学会；
・第４４回日本発生生物学会年会　
　２０１１年５月１８日〜２１日（沖縄、宜野湾市）

タイトル；Six1 and Six4 homeoproteins are required for sex determination in mouse gonad.
　
発表者；藤本　由佳　氏
　　　（熊本大学　発生医学研究所　腎臓発生分野）

Abstract；
Six family genes are mammalian homolog of Drosophila sine oculis, which encodes a transcriptional factor with characteristic homeo-domain and six-domain. We previously reported the cooperative functions of Six1 and Six4 are essential for the kidney formation by analyzing Six1/Six4-deficient mice, whereas Six4-deficient mice have no apparent abnormality. We here reported that the cooperative functions of Six1 and Six4 in the sex determination that male to female sex-reversal was found in the Six1/Six4-deficient gonads due to the impaired Sry and Sox9 expression.
In the E13.5 XY-mutant gonads, the expression of male-specific marker genes (Mis, 3betaHSD, Sox9) was decreased or absent, and female-specific marker genes (Wnt4, Foxl2) expression was increased. On E11.5, when sex-determination gene Sry expression reaches a peak, Sry and subsequent Sox9 expression were down-regulated in the XY-mutant gonads. On E10.5, prior to the Sry expression, we also found that the expression of Fog2 (Friend of GATA-2) but not Lhx9, WT1, M33, Emx2, which are reported to be important for the the induction of Sry expression and subsequent the testis differentiation, was decreased in the E10.5 XY-mutant gonads. We found that Fog2 promoter region have Six1/Six4 binding sequence, and Six1/Six4 may activate Fog2 expression by reporter assay. These findings suggest that Fog2 maybe direct target of Six1/Six4, and decreased expression of Fog2 may lead to the sex-reversal phenotype in the Six1/Six4-deficient mice.
We will discuss the functional relationship between Six1/Six4 and the expression of Fog2.