Ectoderm Formation in the Early Xenopus Embryo

描述（由主要研究者提供）：脊椎动物身体的所有组织均来自三个初级胚层：外胚层、中胚层和内胚层。外胚层产生中枢神经系统和表皮。与其他两个胚层相比，它的发育知之甚少。我们最近已经确定了一个叉头型转录因子，Foxi 1 e，这是从合子转录的开始，产生外胚层的区域，是必不可少的神经系统和表皮的形成。初步和已发表的数据表明，Foxi 1 e是外胚层的一种重要合子激活剂。然而，Foxi 1 e并非在所有形成外胚层的细胞中表达。相反，它以马赛克模式表达，表达细胞与非表达细胞混合。我们已经表明，通过Notch途径的局部信号传导和胚胎植物细胞（形成内胚层）释放的全局信号联合收割机控制Foxi 1 e的表达模式。该项目旨在确定这些信号通路产生Foxi 1 e模式的机制，以及其嵌合表达模式产生胚胎外胚层组织的机制。已经收集了大量的初步数据，包括鉴定Foxi 1 e表达的母体激活子和抑制子，以及胚胎外胚层形成区域中的新型Wnt信号通路，Affytron筛选其表达因胚胎中Foxi 1 e耗尽和Notch信号而改变的基因。在项目结束时，我们的目标是建立，第一次，从鸡蛋到胚胎外胚层组织的分子途径的轮廓。 公共卫生相关性： 身体的所有组织都来自早期胚胎中形成的三层组织。这些被称为三个主要的胚层。外胚层胚层产生脑和脊髓，以及皮肤的表皮。尽管外胚层的重要性，令人惊讶的是，很少有人知道它是如何在胚胎中形成的。利用非洲爪蟾胚胎，我们的目标是建立外胚层形成的分子机制。我们已经确定了一个转录因子，表达在胚胎的区域，将形成外胚层，这是绝对需要的正常发育的大脑脊髓，和表皮。令人惊讶的是，它在前外胚层细胞中以马赛克模式表达;表达细胞与非表达细胞混合，但所有细胞都将继续形成外胚层组织。本项目旨在确定产生镶嵌模式的分子机制，以及转录因子表达的镶嵌模式可以产生外胚层的机制。

DESCRIPTION (provided by Principal Investigator): All tissues of the vertebrate body arise from three primary germ layers; the ectoderm, mesoderm and endoderm. The ectoderm gives rise to the central nervous system and epidermis. Its development is poorly understood, compared with the other two germ layers. We have recently identified a forkhead-type transcription factor, Foxi1e, that is expressed from the start of zygotic transcription in the region that gives rise to the ectoderm, and is essential for formation of both nervous system and epidermis. Preliminary and published data show that Foxi1e is an essential zygotic activator of ectoderm. However, Foxi1e is not expressed in all cells that will form the ectoderm. Instead it is expressed in a mosaic pattern, with expressing cells intermingled with non-expressing cells. We have shown that local signaling through the Notch pathway, and global signals released by the vegetal cells of the embryo (which form the endoderm), combine to control the expression pattern of Foxi1e. This project aims to identify the mechanism by which these signaling pathways generate the pattern of Foxi1e, and the mechanism by which its mosaic expression pattern gives rise to the ectodermal tissues of the embryo. A great deal of preliminary data has been assembled, including the identification of maternal activators and repressors of Foxi1e expression, as well as a novel Wnt signaling pathway in the ectoderm-forming region of the embryo, Affymetrix screens for genes whose expression is changed by Foxi1e depletion in the embryo, and by Notch signaling. At the end of the project we aim to establish, for the first time, the outline of a molecular pathway leading from the egg to the ectodermal tissues of the embryo. PUBLIC HEALTH RELEVANCE: Narrative: All tissues of the body arise from three layers of tissue that form in the early embryo. These are known as the three primary germ layers. The ectoderm germ layer gives rise to the brain and spinal cord, and the epidermis of the skin. Despite the importance of the ectoderm, surprisingly little is known about how it forms in the embryo. Using the Xenopus embryo, we aim to establish the molecular mechanism of ectoderm formation. We have identified a transcription factor, expressed in the region of the embryo which will form the ectoderm, which is absolutely required for normal development of the brain spinal cord, and epidermis. Surprisingly, it is expressed in a mosaic pattern in the pre-ectodermal cells; expressing cells are intermingled with non-expressing cells, and yet all cells will go on to form the ectodermal tissues. This project aims to identify the molecular mechanism that generates the mosaic pattern, and the mechanism by which a mosaic pattern of expression of a transcription factor can give rise to the ectoderm.