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在透镜发育中的功能研究阐明透镜中基因特异表达的上游调控因子对理解透镜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性实验,通过鸡胚卵内电穿孔的方法来建立眼睛发育过程中maf家族基因成员之间的调控联系。根据我的数据,它被发现,早期表达的Maf后表达的成员有一个正向转录控制。值得注意的是,MafB,其表达晚得多,表现出对L-Maf和c-Maf表达的负面影响。所有Maf蛋白都具有转录激活下游基因的多余活性,但受空间和时间特异性机制控制的能力程度不同。我们还发现Maf蛋白在激活眼粘膜中的钙粘蛋白、MIP和连接蛋白中具有不同的功能。Maf对间隙连接和水通道基因的调控是一个新的发现,这使我们能够将Maf视为脊椎动物透镜发育所必需的广泛基因的调节剂。我的研究结果表明,maf基因保持在家庭内的调节机制,其冗余和离散的功能,相对于透镜晶体蛋白和非晶体蛋白基因的表达决定透镜诱导和纤维分化程序。我认为Maf的参与对鸡透镜的发育是至关重要的。目前,我试图通过RT-PCR来概括上述数据,以便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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