Developing vision: Cadherin function in lens morphogenesis

该应用程序的长期目标是了解早期晶状体发育的机制。我们将在了解晶状体诱导的遗传学和信号传导方面取得最新进展的基础上，扩展到晶状体形态发生领域（定义为上皮形状的变化，这是晶状体从晶状体基板到晶状体囊泡发育阶段的关键特征）。我们正在进行的应用的具体目标是旨在解决晶状体发育信号和形态发生如何协调的问题。特别是，我们的初步证据表明n -钙粘蛋白在晶状体形成中具有关键作用。n -钙粘蛋白是一种粘附分子，通过与肌动蛋白细胞骨架的c端连接介导上皮细胞的粘附和形态发生。n -钙粘蛋白也非常有趣，因为它具有激活或增强FGF信号的能力。我们将通过以下几个方面来研究n -钙粘蛋白的功能：目标1，确定n -钙粘蛋白的哪个来源、晶状体外胚层和/或视网膜对晶状体诱导至关重要；目标2，使用分子显位分析将n -钙粘蛋白置于现有的晶状体诱导遗传途径中；目标3，通过评估n -钙粘蛋白在粘附、形态发生和FGF通路信号传导中的作用，确定为什么n -钙粘蛋白是晶状体诱导所必需的。研究n -钙粘蛋白在晶状体诱导中的功能是一个有趣的发育问题，显然，了解晶状体发育的基本机制可以为晶状体疾病的治疗解决提供未来方向的指示。然而，最近有研究表明，n -钙粘蛋白可以促进肿瘤细胞的转移行为。从这个角度来看，我们的研究也将提高我们计划治疗癌症的能力。

The long-term goal of this application is an understanding of the mechanisms of early lens development. We will build on our recent progress in understanding the genetics and signaling of lens induction by extending into the area of lens morphogenesis (defined as the epithelial shape changes that are critical features of lens development from the stage of the lens placode to the lens vesicle). Our specific aims for the ongoing application are designed to address the question of how lens development signaling and morphogenesis are coordinated. In particular, our preliminary evidence has shown that N-cadherin has a critical function in lens formation. N-cadherin is an adhesion molecule that mediates epithelial adhesion and morphogenesis through a C-terminal connection to the actin cytoskeleton. N-cadherin is also very interesting because it has the ability to activate or enhance FGF signaling. We will investigate N-cadherin function by: Aim 1, determining which source(s) of N-cadherin, presumptive lens ectoderm and/or presumptive retina is critical for lens induction, Aim 2, using molecular epistasis analysis to place N-cadherin within the existing genetic pathway for lens induction, Aim 3, determining why N-cadherin is required for lens induction by assessing its role in adhesion, morphogenesis and FGF pathway signaling. Investigation of N-cadherin function in lens induction is an interesting developmental problem, and clearly, an understanding of the basic mechanisms of lens development can provide an indication of future directions for therapeutic resolution of lens disease. However, in addition, it has recently been shown that N-cadherin can contribute to the metastatic behavior of tumor cells. From this point of view, our studies will also enhance our ability to plan therapies for the treatment of cancer.