Molecular basis of Zic proteins-mediated developmental regulation.

Zic 蛋白介导的发育调节的分子基础。

基本信息

批准号：
13480260
负责人：
ARUGA Jun
金额：
$ 9.66万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

In this research project, we investigated following subjects : 1.Clarification of signal transduction pathway controlling the funtion of Zic proteins. 2.Identification of the transcriptioin-activating domain in Zic proteins. 3.Identification of uncharacterized Zic-binding proteins. 4.Understanding the the regulatory mechanism of the identified protein-protein interactions and their significance in the developmental control. 5.Exploration and analysis of the downstream target genes of Zic proteins. As an achievement of the investigation, we revealed following facts : 1.Zic proteins can phycally and functionally interact with Gli proteins, which are the transcriptional mediator of the Hedgehog signal (Koyabu et al., 2001 ; Mizugishi et al., 2001), 2.Zic1 can activate the Notch signaling as indicated by the gain-of-function analysis of Zic1 in chick and mouse spinal cord (Aruga et al., 2002), 3.Novel transcription activating domains were mapped in the N terminal region and zinc finger domain of Zic2 proteins (Mizugishi et al., in press), 4.Severeal Zic-binding proteins was identified by yeast two hybrid assay. The role of interaction in skeletal morphogenesis was investigated as for one of the newly identified Zic proteins. 5.Candidates of the Zic 1 downstream target genes in the course of cerebellar development were identified by microarray analysis (Hoshino et al., 2004). The microarray analysis was also carried out using other Zic mutant mice. Some of the candidate genes were now cleared to be important in the regulation of neuronal development.

在本研究项目中，我们研究了以下课题： 1.阐明控制Zic蛋白功能的信号转导通路。 2.Zic蛋白转录激活结构域的鉴定。 3.未表征的 Zic 结合蛋白的鉴定。 4.了解已识别的蛋白质-蛋白质相互作用的调节机制及其在发育控制中的意义。 5.Zic蛋白下游靶基因探索与分析。作为研究成果，我们揭示了以下事实： 1.Zic 蛋白可以在物理上和功能上与 Gli 蛋白相互作用，Gli 蛋白是 Hedgehog 信号的转录介质（Koyabu 等人，2001；Mizugishi 等人，2001）， 2.Zic1 在小鸡和小鼠脊髓中的功能获得分析表明，Zic1 可以激活 Notch 信号传导（Aruga 等人， 2002），3.在Zic2蛋白的N末端区域和锌指结构域中绘制了新的转录激活结构域（Mizugishi等人，出版中），4.通过酵母二杂交测定鉴定了几种Zic结合蛋白。对于一种新鉴定的 Zic 蛋白，研究了相互作用在骨骼形态发生中的作用。 5.通过微阵列分析鉴定了小脑发育过程中Zic 1下游靶基因的候选基因(Hoshino et al., 2004)。还使用其他 Zic 突变小鼠进行了微阵列分析。一些候选基因现已被证实在神经元发育的调节中发挥着重要作用。