MOLECULAR REGULATION OF EARLY XENOPUS DEVELOPMENT
MOLECULAR REGULATION OF EARLY XENOPUS DEVELOPMENT
批准号:
2200334
负责人:
David Kimelman
金额:
$12.65万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1990
资助国家:
美国
项目状态:
已结题
起止时间:
1990-08-01 至 1995-07-31
关键词:
Xenopus alternatives to animals in research antisense nucleic acid biological signal transduction cell cell interaction density gradient ultracentrifugation developmental genetics early embryonic stage fibroblast growth factor genetic regulation genetic transcription growth factor receptors histogenesis immunoprecipitation mesoderm messenger RNA molecular genetics nonmammalian vertebrate embryology polymerase chain reaction protein degradation transcription factor
中文摘要
脊椎动物胚胎的发育依赖于一个称为
一种利用细胞间通信来指定
构成胚胎身体计划的细胞的精确组织。二
增长因素最近被认为可能是这些因素的调节因素
归纳事件。本提案特别关注以下其中一项的作用
这些是碱性成纤维细胞生长因子(BFGF),因为它既能诱导
形成中胚层细胞类型,存在于早期胚胎中。
我们将从三个方面研究碱性成纤维细胞生长因子介导的中胚层诱导。
1.为了确定中胚层是如何在受限区域形成图案的
在早期胚胎,碱性成纤维细胞生长因子蛋白将被定位。作为中胚层
相反,诱导可能由bFGF的调节分泌控制,即
我们将对早期卵裂球释放碱性成纤维细胞生长因子进行研究。最后,
为了确定bFGF在胚胎中的作用,将抑制其在胚胎中的作用
活体在诱导过程中的作用。
2.新发现的卵母细胞含有反义mRNA,
导致bFGF转录本的共价修饰将进一步
调查以确定此修改是否是机制的一部分
碱性成纤维细胞生长因子转录本的靶向降解。此外,这种蛋白质
由反义转录本编码的将被广泛表征。
3.由于对碱性成纤维细胞生长因子的细胞反应知之甚少
诱导中胚层,表达的RNA的cDNAs拷贝
将分离出碱性成纤维细胞生长因子。在诱导过程中早期转录的基因
将首先研究中胚层的突起或特定部分,
其长期目标是定义基因变化的等级
由bFGF发起。
由于胚胎发生机制的失败导致了出生缺陷,
了解正常的发展路径是很重要的。自.以来
碱性成纤维细胞生长因子S不仅参与了开发调控,还可以将
不同医学领域的共同问题。
英文摘要
Development of the vertebrate embryo is dependent on a process termed
induction in which intercellular communication is utilized to specify the
precise organization of the cells comprising the embryonic body plan. Two
growth factors have been recently identified as likely regulators of these
inductive events. This proposal focuses specifically on the role of one of
these, basic fibroblast growth factor (bFGF), as it both induces the
formation of mesodermal cell types and is present in the early embryo.
Three aspects of bFGF-mediated mesoderm induction will be pursued.
1. In order to determine how mesoderm is patterned in a restricted region
of the early embryo, the bFGF protein will be localized. As mesoderm
induction may instead be controlled by the regulated secretion of bFGF, the
release of bFGF from the early blastomeres will be studied. Finally, the
function of bFGF in the embryo will be inhibited in order to define its in
vivo role in the inductive process.
2. The novel finding that the oocyte contains an anti-sense mRNA that
causes the covalent modification of the bFGF transcript will be further
investigated to determine whether this modification is part of a mechanism
of targeted degradation of the bFGF transcript. In addition, the protein
encoded by the anti-sense transcript will be extensively characterized.
3. As little is known about the cellular response to bFGF during the
induction of mesoderm, cDNA copies of the RNAs expressed in response to
bFGF will be isolated. Genes that are transcribed early in the inductive
process or in a particular part of the mesoderm will be studied initially,
with a long range goal of defining the hierarchy of genetic changes
initiated by bFGF.
As birth defects arise from a failure in the mechanisms of embryogenesis,
it is important to understand the normal pathway of development. Since
bFGF s not only involved in development regulation but can also convert
common issues in different medical fields.
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