Control of Spemann's organizer

描述（由申请人提供）：本提案的长期目标是在我们对信号通路和基因表达如何协作以控制发育中的脊椎动物胚胎中的最早模式化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控制模式生物非洲爪蟾中Spemann组织者形成的机制。Spemann's organizer是一组细胞，它们共同作为中央信号中心，通过图案化中胚层和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，分泌诱导蛋白如头蛋白和脊索蛋白，以及调节形态发生和细胞运动，涉及直接的细胞-细胞接触。因此，组织细胞的一个明确的分子特征是表达特定的信号分子，如帮助其执行功能的脊索蛋白。在组织者细胞内缺乏FGF信号传导的情况下， 诱导蛋白脊索蛋白减少，但包括头蛋白在内的其它组织特异性分子的产生不受影响。此外，由组织者决定的中胚层模式被破坏，但胚胎（头部）中大多数前部神经结构的形成（也需要组织者功能）相对正常。我们推测，FGF信号在组织者细胞内控制组织者的诱导功能的一个重要的子集，至少部分通过控制组织者特异性转录的弦蛋白。我们将通过研究FGF信号通路在组织者中的作用和脊索蛋白的转录来阐述我们的观点，因为它们与Spemann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.