MOLECULAR REGULATION OF EARLY XENOPUS DEVELOPMENT
MOLECULAR REGULATION OF EARLY XENOPUS DEVELOPMENT
批准号:
3328892
负责人:
David Kimelman
金额:
$11.97万
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 1995-03-31
关键词:
Xenopus 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
诱导,其中细胞间的通信被用来指定
构成胚胎体平面的细胞的精确组织。 两
生长因子最近已被确定为这些的可能调节剂,
感应事件 这项建议特别着重于下列机构之一的作用:
这些,碱性成纤维细胞生长因子(bFGF),因为它都诱导
中胚层细胞类型的形成,存在于早期胚胎中。
bFGF介导的中胚层诱导的三个方面将继续进行。
1. 为了确定中胚层是如何在一个有限的区域内形成图案的
在早期胚胎中,bFGF蛋白将被定位。 作为中胚层
相反,诱导可以通过调节bFGF的分泌来控制,
将研究bFGF从早期卵裂球的释放。 最后
bFGF在胚胎中的功能将被抑制,以确定其在胚胎发育中的作用。
在诱导过程中的体内作用。
2. 新的发现是卵母细胞含有反义mRNA,
导致bFGF转录物的共价修饰将进一步
调查以确定这种修饰是否是机制的一部分
bFGF转录物的靶向降解。 此外,蛋白质
将广泛地表征由反义转录物编码的基因。
3. 由于很少有人知道细胞对bFGF的反应,
中胚层的诱导,响应于
将分离bFGF。 在诱导期早期转录的基因
过程或中胚层的特定部分将首先进行研究,
长期目标是定义基因变化的层次
由bFGF发起。
由于出生缺陷是由于胚胎发生机制的失败,
重要的是要了解正常的发展途径。 以来
bFGF不仅参与发育调控,而且还能转化成
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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