DYNAMICS OF THE FOREGUT FORMATION

前肠形成的动力学

基本信息

批准号：
18570205
负责人：
FUKUDA KIMIKO
金额：
$ 2.63万
依托单位：
Tokyo Metropolitan University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18570205/
关键词：
DIGESTIVE TRACT ENDODERM MICROARRAY CELL MOVEMENT REGIONALIZATION CELL LABELLING

项目摘要

In chicken embryo, the definitive endoderm which gives rise to the epithelial lining of the digestive tract is established during gastrulation from epiblast. At the beginning, endoderm forms as an unspecified simple flat-sheet structure, and gradually becomes regionalized into antero-posteriorly and dorso-ventrally divided organs during embryogenesis. Finally, endodermal epithelium in each organ exhibits unique morphologies and gene expression patterns to perform its specific physiological functions. It is reported that the endoderm is necessary for the specification of other tissues such as forebrain, heart and inner ear. Therefore, to understand the detailed mechanisms of the endodermal specification is very helpful in clarifying the whole body plan in vertebrates. However, little is known about mechanisms underlying the initial steps of the regional differentiation (regionalization) in the endoderm. In this thesis I investigated to elucidate the timing of regionalization of endoderm, and molecular mechanisms essential for the early regionalization in endoderm.This study clarified the precise timing of specification in foregut and hindgut endoderm, and based on these results, revealed the expression profile of many novel genes which may be important for the initial regionalization in endoderm. Moreover, the results I obtained that the signaling modifier of BMPs, sizzled, plays an essential role for regionalization of foregut, especially in liver development, illuminate importance of modification of the gradient of secreted molecules in specification of complex morphogenesis. The study presented here must provide a framework for further elucidation of molecular mechanisms underlying the differentiation along the body axis at early stage development not only in endoderm, but also whole body of the vertebrate.

在鸡胚胎中，产生消化道上皮内层的定形内胚层是在外胚层原肠胚形成过程中形成的。起初，内胚层形成为未特指的简单平板结构，并在胚胎发生过程中逐渐区域化为前后和背腹分开的器官。最后，每个器官的内胚层上皮表现出独特的形态和基因表达模式以执行其特定的生理功能。据报道，内胚层对于前脑、心脏和内耳等其他组织的发育是必需的。因此，了解内胚层规范的详细机制对于阐明脊椎动物的整体规划非常有帮助。然而，人们对内胚层区域分化（区域化）初始步骤的机制知之甚少。在本论文中，我研究了阐明内胚层区域化的时间，以及内胚层早期区域化所必需的分子机制。本研究阐明了前肠和后肠内胚层规范化的精确时间，并基于这些结果，揭示了许多新基因可能对内胚层的初始区域化很重要。此外，我得到的结果是，BMP 的信号调节剂，嘶嘶声，对于前肠的区域化发挥着重要作用，特别是在肝脏发育中，阐明了在复杂形态发生规范中分泌分子梯度调节的重要性。这里提出的研究必须提供一个框架，以进一步阐明不仅在内胚层而且在脊椎动物整个身体的早期发育阶段沿着身体轴分化的分子机制。