Investigating the Interplay Between WNT and FGF Signaling in Prostate Initiation

描述（由申请人提供）：本研究的长期目标是了解前列腺形成和维持的分子机制。前列腺一直是密集的生物医学研究的主题，不仅因为它在性功能中的关键作用，而且更因为人类前列腺疾病的高发病率。尽管努力，一个方面仍然知之甚少的是前列腺启动的分子机制，这是拟议的研究的重点。迄今为止，除了雄激素途径之外，只有一种信号传导途径，即成纤维细胞生长因子（FGF）途径已在遗传学上被证明对所有前列腺芽的起始是必不可少的。在这个建议中，我们提出的初步数据表明，WNT信号是必不可少的前列腺启动。从我们最近在肺（与前列腺相似的分支器官）中的发现中，我们假设WNT在前列腺起始中的功能是通过其对FGF信号传导的调节来介导的。我们将使用先进的遗传学方法来解决这两个信号通路之间的关系，在前列腺发育的这一重要的第一步。该提案定义了一项长期战略的开始，以解剖前列腺发育和稳态所必需的信号网络。公共卫生相关性：该提案旨在定义WNT和FGF信号传导如何共同控制前列腺形成。由于这两种途径都是干细胞维持和前列腺肿瘤发生的核心，我们的发现将为未来研究它们在前列腺发病机制中的相互作用提供基础。

DESCRIPTION (provided by applicant): The long-term objective of this study is to understand the molecular mechanism of prostate formation and maintenance. The prostate has been the subject of intense biomedical research not only because of its key role in sexual function, but more because of the high incidence of human prostate diseases. Despite the effort, one aspect that has remained poorly understood is the molecular mechanism of prostate initiation, and this is the focus of the proposed study. To date, in addition to the androgen pathway, only one signaling pathway, the Fibroblast Growth Factor (FGF) pathway has been genetically demonstrated to be essential for the initiation of all prostate buds. In this proposal, we present preliminary data suggesting that WNT signaling is essential for prostate initiation. Drawing from our recent findings in the lung, a similar branching organ as the prostate, we hypothesize that WNT function in prostate initiation is mediated through its regulation of FGF signaling. We will use advanced genetic approaches to address the relationship between these two signaling pathways in this essential first step of prostate development. This proposal defines the beginning of a long-term strategy to dissect the signaling network essential for the development and homeostasis of the prostate. PUBLIC HEALTH RELEVANCE: This proposal aims to define how WNT and FGF signaling function together to control prostate formation. As both pathways are central to stem cell maintenance and prostate tumorigenesis, our finding will provide the basis for future investigation of their interaction in prostate pathogenesis.