水晶体形成におけるMaf転写因子ファミリーの機能多様性の解析
水晶体形成におけるMaf転写因子ファミリーの機能多様性の解析
批准号:
17791233
负责人:
H.M Reza
金额:
$2.18万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Young Scientists (B)
财政年份:
2005
资助国家:
日本
项目状态:
已结题
起止时间:
2005 至 2006
中文摘要
Maf在晶状体发育中的功能分析阐明晶状体中基因特异性表达的上游因子对了解晶状体的形态发生具有重要意义。我一直在进行一系列的功能获得实验,通过鸡胚胎卵内电穿孔来建立maf家族基因成员在眼睛发育过程中的调节联系。根据我的数据,发现早期表达的Maf对后期表达的成员具有正向转录控制。值得注意的是,表达较晚的MafB对L-Maf和c-Maf的表达有负面影响。所有的Maf蛋白在传递下游基因时都有一些多余的活性,但它们的能力程度不同,受空间和暂时特异性机制的控制。我们还发现Maf蛋白在激活眼连笼中的钙粘蛋白、MIP和连接蛋白方面具有独特的功能。Maf对间隙连接和水通道基因的调控是一项新发现,使我们能够将Maf视为脊椎动物晶状体发育所必需的广泛基因的调节器。我的研究结果表明,maf基因在该家族中保持着一种调控机制,它们在晶状体结晶蛋白和非结晶蛋白基因表达方面的冗余和离散功能决定了晶状体诱导和纤维分化程序。我认为Maf的参与对小鸡晶状体发育至关重要。目前,我试图通过RT-PCR概括上述数据,以更好地论证这一概念。
英文摘要
Functional analysis of Maf in lens developmentElucidation of upstream factors responsible for specific expression of genes in lens is important to understand the morphogenesis of lens. I have been performing a series of gain-of-function experiments to establish a regulatory link among the members of maf family genes during eye development by in ovo electroporation in chick embryos. Based on my data, it is found that early-expressed Maf has a forward transcriptional control on later-expressed members. Notably, MafB, which is expressed much later, exhibits a negative effect on L-Maf and c-Maf expressions. All Maf proteins have some superfluous activities in transiactivating downstream genes yet they are different by their degrees of ability controlled by spatially and temporarily specific mechanisms. We have also found distinct functions of Maf proteins in activating Cadherin, MIP, and Connexins in eye lincage. Regulation of gap junction and water channel genes by Maf is a novel finding that enables us to consider the Maf as a regulator of wide range of genes essential for vertebrate lens development. My results demonstrate that maf genes maintain a regulation mechanism within the family and, their redundant and discrete functions with respect to the expression of lens crystallin and non-crystallin genes determine lens induction and fiber differentiation programs. I suggest that the involvement of Maf is critical for chick lens development Currently, I am trying to recapitulate the above data by RT-PCR for better argument for the notion.
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