Ectoderm Formation in the Early Xenopus Embryo

描述（由首席研究员提供）：脊椎动物身体的所有组织都来自三个初级胚层；外胚层、中胚层和内胚层。外胚层产生中枢神经系统和表皮。与其他两种胚层相比，它的发育鲜为人知。我们最近发现了一种叉头型转录因子Foxi1e，它从合子转录开始就在产生外胚层的区域表达，对神经系统和表皮的形成都是必不可少的。初步和已发表的数据表明，Foxi1e是外胚层重要的合子激活剂。然而，Foxi1e并不是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在一起。我们已经证明，通过Notch通路的局部信号和胚胎（形成内胚层）的营养细胞释放的全局信号共同控制Foxi1e的表达模式。本项目旨在确定这些信号通路产生foxxi1e模式的机制，以及foxxi1e嵌合表达模式产生胚胎外胚层组织的机制。Affymetrix已经收集了大量的初步数据，包括鉴定母体foxxi1e表达的激活因子和抑制因子，以及胚胎外胚层形成区域的新Wnt信号通路，Affymetrix筛选胚胎中foxxi1e缺失和Notch信号通路改变表达的基因。在项目结束时，我们的目标是首次建立从卵子到胚胎外胚层组织的分子途径的轮廓。

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.