权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Notch Signaling and Lens Development

缺口信号和镜头开发

基本信息

批准号：
7506442
负责人：
PUMIN ZHANG
金额：
$ 38.38万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7506442
关键词：
Anterior Applications Grants Area Beckwith-Wiedemann Syndrome Binding Sites CDKN1C gene Cell Cycle Cell Differentiation process Cells Crystalline Lens Crystallins Data Development Developmental Biology Ectoderm England Epithelial Cells Epithelium Equilibrium FGFR1 gene FGFR3 gene Family Feedback Fibroblast Growth Factor Fibroblast Growth Factor 1 Figs - dietary Future Gene Expression Generations Genes Growth Growth and Development function Head In Vitro Left Lens Fiber Lens Placodes Ligands Location Maps Mediating Mitotic Mus Nature Neuroectoderm Notch Signaling Pathway Pathway interactions Play Positioning Attribute Process Retina Role Secondary to Signal Transduction Staging Surface Testing Transcription Repressor/Corepressor Transgenic Mice Undifferentiated Vesicle Withdrawal base cyclin-dependent kinase inhibitor 1B emerging adult extracellular fiber cell in vivo inhibitor/antagonist lens lens morphogenesis member migration mutant notch protein overexpression premature prevent progenitor promoter receptor research study ward

项目摘要

Our recent studies indicate that the Notch signaling pathway inhibits lens fiber cell differentiation. We found that Herp2, a transcriptional repressor and an effector of Notch signaling, was expressed in lens epithelium adjacent to the transition zone. When Notch signaling was disrupted specifically in the lens, Herp2 expression was lost and the lens epithelial cells prematurely differentiated [1]. How does Notch signaling block lens fiber cell differentiation? We propose that Herp2 suppresses the expression of genes that play critical roles in the formation of lens fiber cells. In support of that, we found p57Kip2, a Cdk inhibitor required for the cell cycle withdrawal during lens fiber cell differentiation [2, 3], was a transcriptional target of Herp2. In this revised proposal, we will further the understanding of how Herp2 suppresses p57 expression in vitro and in vivo. In addition, our recent experiments uncovered Prox1 and alphaA crystallin as potential targets of Herp2. Since these two genes are known regulators of lens fiber cell differentiation, by suppressing their expression, Herp2 (hence the Notch signaling) prevents the differentiation. We will validate this initial finding with in vitro and in vivo experiments.

我们最近的研究表明，Notch信号通路抑制晶状体纤维细胞的分化。我们发现在邻近过渡区的晶状体上皮细胞中表达了转录抑制因子和Notch信号的效应因子Herp2。当Notch信号在晶状体中被破坏时，Herp2的表达丢失，晶状体上皮细胞过早分化[1]。Notch信号如何阻止晶状体纤维细胞分化？我们认为Herp2抑制了在晶状体纤维细胞形成中起关键作用的基因的表达。为了支持这一点，我们发现p57Kip2，一种在晶状体纤维细胞分化过程中细胞周期退出所需的CDK抑制物[2，3]，是Herp2的转录靶点。在这份修订后的提案中，我们将进一步了解Herp2如何在体外和体内抑制p57的表达。此外，我们最近的实验发现Prox1和AlphaA晶体蛋白是Herp2的潜在靶点。由于这两个基因是已知的晶状体纤维细胞分化的调节基因，通过抑制它们的表达，Herp2(因此是Notch信号)阻止了分化。我们将通过体外和体内实验来验证这一初步发现。