REGULATION OF VERTEBRATE DEVELOPMENT BY MATERNAL MRNA

母体 mRNA 对脊椎动物发育的调节

• 批准号: 3468938
• 负责人: H. Joseph Yost
• 金额: $ 9.26万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3468938
• 关键词: RNA binding protein; Xenopus oocyte; antisense nucleic acid; cell differentiation; cytogenetics; developmental genetics; embryogenesis; histogenesis; messenger RNA; microinjections; northern blottings; nucleic acid sequence; protein structure function; transcription factor; vertebrate embryology

All animals start life as a single cell, the fertilized egg. Through the process of embryonic development, the fertilized egg divides into hundreds of different cell types arranged in highly complex and well-organized patterns. The long term objective of the proposed research is to apply modem molecular and embryological techniques to address an age-old question: how are the fundamental body plans in humans and animals formed? The specific goal of this research is to identify the processes and molecules that are involved in orchestrating the first steps of vertebrate embryonic development. It is known that some of the information required for development is put into the egg as maternal messenger RNA (mRNA) molecules that initiate complex patterns of gene expression. It is also known in Xenopus that a small group of specialized cells in the dorsal region of an embryo plays a central role in development, by providing the instructions necessary to 'organize' the rest of the embryo into a normally formed animal. A class of mRNA molecules that are found only in cells of this specialized dorsal region of the embryo has been cDNA cloned and is being characterized. The research proposed here has two specific aims. First, by analyzing the distribution of mRNA species in different regions of the embryo and by following the fate of modified mRNAs microinjected into embryos, it will identify the cellular and molecular mechanisms that result in the localization of this special class of maternal mRNAs. This analysis will greatly increase our ability to trace the biological cascade from fertilization to vertebrate pattern formation. Second it is now possible using microinjection of antisense oligonucleotides to specifically eliminate a maternal mRNA species within an oocyte, then to mature and fertilize the egg in vitro to assess the effects on the developing embryo. This powerful molecular embryology technique will be used to investigate the function(s) of these dorsally localized maternal mRNAs in development In light of the unique 'organizing' role of the dorsal region, it is likely that this analysis will increase our understanding of human congenital malformations on a molecular level. This study will greatly deepen our understanding of gene regulation and the fundamental mechanisms underlying vertebrate development, cellular differentiation and pattern formation.

所有动物都是以单个细胞--受精卵的形式开始生命的。通过 胚胎发育过程中，受精卵分为 数百种不同类型的细胞排列成高度复杂和 组织严密的模式。建议的长远目标 研究是将现代分子和胚胎学技术应用于 回答一个古老的问题：人类的基本身体计划是如何 动物形成了吗？ 这项研究的具体目标是确定流程和 参与编排第一步的分子 脊椎动物胚胎发育。据了解，其中一些 发育所需的信息作为母体放入卵子中 启动基因复杂模式的信使RNA(MRNA)分子 表情。在非洲爪哇，也知道有一小群 胚胎背部的特殊细胞起着中心作用。 在开发中，通过提供必要的指令来“组织” 将胚胎的其余部分转化为正常形成的动物。一类信使核糖核酸 仅在这种特殊背部区域的细胞中发现的分子 已经克隆了胚胎的DNA，并正在进行鉴定。这个 这里提出的研究有两个具体目标。首先，通过分析 MRNA在胚胎不同区域的分布及其在胚胎发育中的作用 在显微注射到胚胎中的修饰的mRNA的命运之后，它将 找出细胞和分子机制，导致 这类特殊的母体mRNAs的本地化。这一分析将 极大地提高了我们追踪生物瀑布的能力 受精到脊椎动物模式的形成。其次，它现在是可能的 利用微量注射反义寡核苷酸来特异性地 消除卵母细胞中的母体mRNA物种，然后成熟和 在体外使卵子受精，以评估对发育的影响 胚胎。这项强大的分子胚胎学技术将被用于 研究这些背侧定位的母体mRNAs在脑内的功能(S) 背部独特的“组织”作用下的发育 地区，这一分析很可能会增加我们对 人类先天畸形的分子水平。这项研究将 极大地加深了我们对基因调控和基本原理的理解 脊椎动物发育、细胞分化的机制 和图案的形成。