Control of Spemann's organizer

描述(由申请人提供)：这项建议的长期目标是在我们对信号通路和基因表达如何协作控制发育中的脊椎动物胚胎中最早的模式事件的理解方面取得进展。为此，我们正在结合分子和胚胎学实验来阐明在模式生物非洲爪哇中控制Spemann组织者形成的机制。Spemann的组织者是一组细胞，它们共同充当中央信号中心，通过形成中胚层的图案并诱导神经组织来建立脊椎动物的身体计划。组织者通过两种机制影响周围细胞的命运，诱导蛋白的分泌，如noggin和chordin，以及涉及细胞与细胞直接接触的形态发生和细胞运动的调节。因此，组织者细胞的一个决定性的分子特征是表达特定的信号分子，如帮助其执行其功能的Chordin。在组织者细胞内没有成纤维细胞生长因子信号的情况下，产生 诱导蛋白质Chordin减少，但包括noggin在内的其他组织特异性分子的产生不受影响。此外，组织者所支配的中胚层图案被破坏，但胚胎(头部)中大多数前部神经结构的形成相对正常，这也需要组织者的功能。我们假设，组织者细胞内的成纤维细胞生长因子信号控制着组织者诱导功能的一个重要子集，至少部分是通过控制组织者特有的Chordin转录。我们将通过研究成纤维细胞生长因子信号通路(S)在组织者中的作用以及Chordin的转录来阐述我们的观点，因为它们与Spemann的组织者的最终诱导功能有关。

DESCRIPTION (provided by applicant): The long-term goal of this proposal is to make advances in our understanding of how signaling pathways and gene expression collaborate to control the earliest patterning events in the developing vertebrate embryo. Toward this end, we are combining molecular and embryological experiments to elucidate the mechanisms that control the formation of Spemann's organizer in the model organism Xenopus laevis. Spemann's organizer is a group of cells that collectively act as the central signaling center that establishes the vertebrate body plan by patterning the mesoderm and inducing neural tissue. The organizer influences the fate of surrounding cells by two mechanisms, the secretion of inducing proteins such as noggin and chordin and the regulation of morphogenesis and cell motility that involves direct cell-cell contacts. Therefore a defining molecular feature of organizer cells is the expression of specific signaling molecules such as chordin that help it perform its functions. In the absence of FGF signaling within the cells of the organizer, production of the inducing protein chordin is diminished, but the production of other organizer-specific molecules including noggin is not effected. In addition mesodermal patterning dictated by the organizer is disrupted, but the formation of most anterior neural structures in the embryo (head), which also require organizer function, is relatively normal. We hypothesize that FGF signaling within the organizer cells controls an important subset of the organizer's inducing functions at least in part through controlling organizer-specific transcription of chordin. We will address our view by examining the role(s) of FGF signaling pathway(s) within the organizer and the transcription of chordin as they relate to the ultimate inducing functions of Spemann's organizer.