Sry and Signals Controlling the Origin and Specification of Sertoli Cells

卡佩尔博士实验室的目标是了解男性性别决定基因Sry是如何控制睾丸器官发生的。SRY被认为在支持细胞的前体细胞中表达，支持细胞被认为通过协调男性特有的器官发育在性别决定中发挥核心作用。最近，她使用DiI对微量支持细胞进行了传代，并表明它们起源于增殖期性腺的体腔上皮，一个细胞可以产生一个支持细胞，而另一个睾丸体细胞可以产生支持细胞。原位表达数据表明，这种不对称的命运决定是由Notch/Delta途径控制的。为了研究这种可能性，将通过腺病毒感染在器官培养中引入结构性Notch基因，以测试Notch的过度表达是否扰乱了对Sertoli细胞命运的承诺。XX Sry转基因实验表明，性腺中的雄性特异性增殖依赖于Sry。为了确定Sry对增殖的影响是否是细胞自主和/或非细胞自主的，我们将分析XX_SYGFP嵌合性腺的增殖。为了探索中肾小管代表Sertoli前体的另一个来源的观点，将产生一种在小管特异启动子控制下携带绿色荧光蛋白报告基因的转基因小鼠。小管细胞将被GFP标记，这样就可以分析这些细胞的命运。阐明男性性别决定开关Sry在生物和形态发生过程中的功能，如细胞命运决定、增殖和细胞重组，将为控制器官发生和分化的分子遗传学机制提供新的信息。

The goal of Dr. Capel's lab is to learn how the male sex determining gene, Sry, controls organogenesis of the testis. Sry is thought to be expressed in precursors of Sertoli cells, the cells believed to play a central role in sex determination by orchestrating male-specific organ development. Recently she has used DiI to lineage trace Sertoli cells and have shown that they arise from the coelomic epithelium of the gonad during a phase of proliferation, a single cell can give rise to a Sertoli and another somatic cell of the testis. In situ expression data suggests that this asymmetric fate decision is under the control of the Notch/Delta pathway. To investigate this possibility, a constitutive Notch gene will be introduced by adenovirus infection in organ culture to test whether overexpression of Notch disrupts commitment to the Sertoli cell fate. XX Sry transgenic experiments show that male-specific proliferation in the gonad depends on Sry. To determine whether Sry's effect on proliferation is cell autonomous and/or non-cell autonomous, proliferation in an XX_SYGFP chimeric gonad will be analyzed. To explore a view in the field that mesonephric tubules represent another source of Sertoli precursors, a transgenic mouse carrying a green fluorescent protein reporter gene under the control of a tubule-specific promoter will be generated. Tubule cells will be marked by GFP such that the fate of these cells can be analyzed. Elucidating the function of the male sex determining switch, Sry, in biological and morphogenetic processes like cell fate decisions, proliferation, and cell reorganization will provide novel information about the molecular genetic mechanisms controlling organogenesis and differentiation.