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如何控制睾丸的器官形成。 Sry被认为在支持细胞的前体中表达，支持细胞被认为通过协调男性特异性器官的发育在性别决定中发挥核心作用。 最近，她使用DiI对支持细胞进行谱系追踪，并表明支持细胞在增殖阶段来自性腺的体腔上皮，单个细胞可以产生支持细胞和睾丸的另一个体细胞。 原位表达数据表明，这种不对称的命运决定是在Notch/Delta途径的控制下。 为了研究这种可能性，将通过腺病毒感染在器官培养物中引入组成型Notch基因，以测试Notch的过表达是否破坏对支持细胞命运的定型。 XX Sry转基因实验表明，雄性特异性的生殖腺增殖依赖于Sry。 为了确定Sry对增殖的影响是细胞自主的和/或非细胞自主的，将分析XX_SYGFP嵌合性腺中的增殖。 为了探索中肾小管代表支持前体的另一来源的观点，将产生在小管特异性启动子控制下携带绿色荧光蛋白报告基因的转基因小鼠。 肾小管细胞将被GFP标记，从而可以分析这些细胞的命运。 阐明男性性别决定开关Sry在生物学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，将提供有关控制器官发生和分化的分子遗传机制的新信息。

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.