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DETERMINATION OF EMBRYONIC POLARITY

胚胎极性的测定

基本信息

批准号：
6180987
负责人：
VIRGINIA E. PAPAIOANNOU
金额：
$ 24.68万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-08-01 至 2001-07-31
项目状态：
已结题

项目摘要

During the early stages on embryonic development, the formation of the embryonic axis is initiated at one pole of the embryo. Most of what is known about the molecular mechanisms underlying this process is based on amphibian embryos, where maternally-derived determinants control this polarity. In amniotes (birds and mammals) this is unlikely because embryos at much later stages can initiate axis formation at any position. Here, the mechanisms that determine embryonic polarity in the early stages of development will be studied using the chick embryo as a model, because of their ease of manipulation and culture. First, the role of the hypoblast (which had been suggested to be responsible for polarity determination) will be tested directly. Then, the region homologous to the amphibian "Nieuwkoop center" (which has been shown in frogs to determine the position of future "organizer" and axial cells) will be located. Finally, a number of genes already found to be expressed in a way that predicts the future polarity of the embryo will be placed in hierarchial order, taking advantage of the fact that portions of the embryo will initiate axis formation when isolated from the rest of the embryo. The results of this project will be of value in suggesting how the molecular cascades that have been implicated in the early development of lower vertebrates (fish, amphibians) can be applied to higher vertebrates (birds and mammals). Potentially, knowledge of these cascades could lead to the development of new molecular diagnostic tools for some of the many serious congenital disorders that affect the early development of the embryonic axis, and may help determine whether monozygotic and conjoined twinning are likely to have a molecular basis.

在胚胎发育的早期阶段，胚轴在胚胎的一极启动。大部分都是已知的这一过程背后的分子机制是基于在两栖类胚胎上，母系衍生的决定因素控制着这一点两极。在羊膜动物(鸟类和哺乳动物)中，这是不太可能的，因为胚胎在更晚的阶段可以在任何时候启动轴的形成位置。在这里，决定胚胎极性的机制早期发育阶段的研究将使用鸡胚胎作为一个模特，因为他们易于操纵和文化。首先，亚爆的作用(曾被认为是负责极性确定)将直接进行测试。然后, 与两栖动物“Nieuwkoop中心”同源的区域(有已经在青蛙身上展示过，以确定未来“组织者”的位置轴单元)将被定位。最后，已经发现了一些基因以一种能预测胚胎未来极性的方式表达将按层次顺序放置，利用以下事实当胚胎的部分分离出来时，会启动轴的形成胚胎的其余部分。这个项目的结果将有价值地建议如何与早期发展有牵连的分子级联低等脊椎动物(鱼、两栖动物)的脊椎动物(鸟类和哺乳动物)。潜在地，对这些的了解级联可能导致新的分子诊断工具的开发对于许多严重的先天性疾病中的一些，影响早期胚轴的发育，并可能有助于确定同卵双胞胎和连体双胞胎可能有分子基础。