Comparative Mechanisms Of Gonad Organogenesis in the Red-Eared Slider Turtle (Trachemys scripta)

红耳龟（Trachemys scripta）性腺器官发生的比较机制

• 批准号: 0317234
• 负责人: Blanche Capel
• 金额: --
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0317234&HistoricalAwards=false
• 关键词: Comparative; Mechanisms; Gonad; Organogenesis; Red

0317234CapelThe primary step in vertebrate sex determination is the initiation of testis development in the bipotential gonad primordium. In mammals this switch operates through the Y-linked gene, Sry. In the red-eared slider turtle, as in many reptiles, the incubation temperature of the egg determines the fate of the gonad. Despite this difference, the structure of the adult testis is highly conserved among species. This observation led to the hypothesis that, although the switch initiating the testis pathway is variable, the pathways downstream that lead to the morphological development of testis cords and the differentiation of testis cell types would be conserved. Surprisingly, recent work in the lab has indicated that the organization of cells into testis structure occurs in a completely different manner in T.scripta. The main goal of this proposal is to understand how molecular signals are deployed and cellular processes are integrated to produce a testis in T.scripta compared to how these processes work in mammals. A number of molecular and cellular pathways have been defined that intersect in the testis determination process in mammals. This work will focus on the roles of three of these independent, yet mutually interactive, components of the sex determination process: cell signaling molecules, cell proliferation, and primordial germ cells. First the roles of cell signaling components of the mammalian sex determination pathway (Fgf9, Dhh, Ptc1, Pdgfra,Wnt4, Fts, and Bmp2) will be investigated in T.scripta and their hierarchical relationship to structural and cellular differentiation of the testis or ovary will be determined. Next, the role of proliferation in T.scripta will be determined by blocking proliferation before, during, and after the temperature sensitive window and determining the effect on sex determination. Third, the role of primordial germ cells in organogenesis of the testis and ovary in T.scripta will be investigated by depleting germ cells before, during, and after the temperature sensitive window and determining the effect on sex determination. This project will advance discovery while providing an excellent training opportunity for graduate students and post-doctoral fellows interested in using comparative approaches to study development and gene function. Results will be broadly disseminated through meetings and publications and the reagents produced will be freely distributed to investigators in the field. The mechanism of sex determination in temperature dependent systems has been a long-standing puzzle in biology. In this work, the signaling processes involved will be investigated and ordered with respect to the temperature switch and hormonal regulation. The work will have direct intellectual application to the question of how temperature-dependent sex determination works, and will enhance the study of mammalian sex determination as well. In addition, it will have broader relevance for the fields of cell signaling, morphogenesis, organogenesis, germ cell biology, proliferation, and the evolution of developmental systems.

[0317234]在脊椎动物性别决定的最初步骤是双电位性腺原基中睾丸发育的开始。在哺乳动物中，这种开关通过y连锁基因Sry起作用。和许多爬行动物一样，在红耳龟中，卵的孵化温度决定了性腺的命运。尽管存在这种差异，但成年睾丸的结构在物种中是高度保守的。这一观察结果导致了这样一种假设，即尽管启动睾丸通路的开关是可变的，但导致睾丸索形态发育和睾丸细胞类型分化的下游通路将是保守的。令人惊讶的是，最近在实验室的工作表明，在scripta中，细胞组织成睾丸结构的方式完全不同。本提案的主要目标是了解分子信号是如何部署的，细胞过程是如何整合的，从而在T.scripta中产生睾丸，比较这些过程在哺乳动物中的工作方式。在哺乳动物睾丸决定过程中，许多分子和细胞途径已经被确定。这项工作将集中在性别决定过程中三个独立但相互作用的组成部分的作用：细胞信号分子、细胞增殖和原始生殖细胞。首先，我们将研究哺乳动物性别决定通路的细胞信号成分（Fgf9、Dhh、Ptc1、Pdgfra、Wnt4、Fts和Bmp2）在T.scripta中的作用，并确定它们在睾丸或卵巢结构和细胞分化中的等级关系。接下来，我们将通过在温度敏感窗口之前、期间和之后阻断T.scripta的增殖，并确定对性别决定的影响，来确定增殖在T.scripta中的作用。第三，通过在温敏感窗前、温敏感窗中和温敏感窗后对原始生殖细胞的消耗和对性别决定的影响，探讨原始生殖细胞在黄颡鱼睾丸和卵巢器官发生中的作用。该项目将促进发现，同时为有兴趣使用比较方法研究发育和基因功能的研究生和博士后提供良好的培训机会。结果将通过会议和出版物广泛传播，制作的试剂将免费分发给外地的调查人员。温度依赖系统的性别决定机制一直是生物学中一个长期存在的难题。在这项工作中，所涉及的信号过程将被调查和排序有关温度开关和激素调节。这项工作将对温度依赖性性别决定如何起作用的问题有直接的智力应用，并将加强对哺乳动物性别决定的研究。此外，它将在细胞信号传导、形态发生、器官发生、生殖细胞生物学、增殖和发育系统进化等领域具有更广泛的相关性。