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Notch Signaling and Lens Development

缺口信号和镜头开发

基本信息

批准号：
7843625
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 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7843625
关键词：
Address Anterior Area CDKN1C gene Cataract Cell Cycle Cell Cycle Regulation Cell Differentiation process Cells Crystalline Lens Crystallins Defect Development Differentiation and Growth EP300 gene Ectoderm Epithelial Cells Epithelium Equilibrium Eye diseases Feedback Fibroblast Growth Factor Figs - dietary Floods Future Gene Expression Genes Goals Growth Head In Vitro Knowledge Left Lens Fiber Lens Placodes Ligands Location Maps Medical center Microphthalmos Mitotic Modeling Mus Neuroectoderm Notch Signaling Pathway Organ Pathway interactions Play Positioning Attribute Prevention Process Publishing Research Project Grants Retina Role Secondary to Signal Transduction Site Staging Surface Testing Texas Time Transcription Repressor/Corepressor Undifferentiated Vesicle Withdrawal base emerging adult fiber cell in vivo inhibitor/antagonist interest lens migration mutant notch protein overexpression premature prevent progenitor 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信号通路抑制透镜纤维细胞的分化。我们发现，Herp2，一个转录抑制因子和Notch信号的效应子，在邻近过渡区的透镜上皮中表达。当Notch信号在透镜中被特异性破坏时，Herp2表达丧失，透镜上皮细胞过早分化[1]。Notch信号如何阻断透镜纤维细胞分化？我们认为Herp 2抑制了在透镜纤维细胞形成中发挥关键作用的基因的表达。为了支持这一点，我们发现p57 Kip 2是Herp 2的转录靶点，p57 Kip 2是透镜纤维细胞分化期间细胞周期退出所需的Cdk抑制剂[2，3]。在这个修订后的建议，我们将进一步了解如何Herp2抑制p57表达在体外和体内。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透镜纤维细胞分化的调节因子，通过抑制它们的表达，Herp2（因此Notch信号传导）阻止分化。我们将通过体外和体内实验验证这一初步发现。