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REGULATION OF VERTEBRATE DEVELOPMENT BY MATERNAL MRNA

母体 mRNA 对脊椎动物发育的调节

基本信息

批准号：
2676526
负责人：
H. Joseph Yost
金额：
$ 5.68万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-08-01 至 1999-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2676526
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

项目摘要

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.

所有的动物都是从一个单细胞即受精卵开始生命的。通过在胚胎发育的过程中，受精卵分裂成数百种不同的细胞类型排列成高度复杂的，组织良好的模式。拟议的长期目标研究是应用现代分子和胚胎学技术，解决一个古老的问题：人类的基本身体计划是如何实现的？动物形成？这项研究的具体目标是确定过程和这些分子参与了脊椎动物胚胎发育据了解，一些发育所需的信息作为母体被放入卵中，信使RNA（mRNA）分子，启动基因的复杂模式表情在非洲爪蟾中也有一小群胚胎背部区域的特化细胞起着核心作用在开发中，通过提供必要的指令来“组织” 胚胎的其余部分变成正常的动物。一类mRNA 这种分子只存在于这个特殊的背部区域的细胞中胚胎的cDNA已被克隆，并正在进行表征。的这里提出的研究有两个具体目标。首先，通过分析 mRNA种类在胚胎不同区域的分布，根据显微注射到胚胎中的修饰mRNA的命运，确定导致这类特殊的母体mRNA的定位。该分析将大大提高了我们追踪生物级联的能力，受精到脊椎动物模式的形成。其次，现在有可能使用反义寡核苷酸的显微注射，消除卵母细胞内的母体mRNA种类，然后成熟，让卵子在体外受精，以评估对发育的影响。胚胎这种强大的分子胚胎学技术将用于研究这些背侧定位的母体mRNAs的功能，根据背侧肌独特的“组织”作用，这一分析可能会增加我们的理解。人类先天畸形的分子水平。本研究将极大地加深了我们对基因调控的理解，脊椎动物发育、细胞分化的机制和模式形成。