Analysis of FGF receptor signalling involved in lens cell proliferation and differentiation

FGF受体信号参与晶状体细胞增殖和分化的分析

• 批准号: nhmrc : 107297
• 负责人: Prof Frank Lovicu
• 金额: $ 22.87万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/analysis-fgf-receptor-proliferation-differentiation/82637
• 关键词: Analysis; FGF; receptor; signalling; involved

Cataract, the loss of transparency of the eye lens, is the leading cause of blindness in the world. An eventual cure for cataract depends on a better understanding of the basic molecular processes in the normal and cataractous lens. Our research has focussed on identifying the molecules that control the formation and maintenance of the lens. Growth factors are important regulators of cell behaviour and our studies have provided compelling evidence that members of the FGF growth factor family play pivotal roles in lens developmental biology by influencing lens cell proliferation and differentiation. An important finding from our laboratory is that FGF induces lens epithelial cell proliferation and differentiation at different concentrations. The FGFs elicit intracellular responses upon binding to and activating cell surface FGF receptors (FGFRs). The FGFRs are membrane bound tyrosine kinases which upon activation, activate specific signalling pathways leading to a specific cellular response. To understand how FGFs mediate and regulate different responses in lens cells, namely cell proliferation and fibre differentiation, we plan to examine the role of FGFRs in normal lens development using genetically altered FGFRs that will be expressed specifically in lenses of transgenic mice. While it is known that four different FGF receptor genes are expressed by the normal developing lens, it is unknown what role each of these play in the process of lens cell proliferation and differentiation. In addition, as we can reproduce a specific FGF-induced lens cellular response in vitro, we will use our lens explant culture system to dissect the signalling pathway(s) downstream from specific receptor activation and correlate this with a specific cellular response. By identifying the molecules and mechanisms that control the cellular processes essential for normal lens development, we can better understand how disruptions of these processes lead to cataract formation.

白内障，即眼球晶状体失去透明度，是世界上致盲的主要原因。白内障的最终治愈取决于对正常晶状体和白内障晶状体的基本分子过程有更好的了解。我们的研究集中在识别控制晶状体形成和维持的分子。生长因子是细胞行为的重要调节因子，我们的研究提供了令人信服的证据，证明FGF生长因子家族成员通过影响晶状体细胞的增殖和分化，在晶状体发育生物学中起着关键作用。我们实验室的一个重要发现是FGF在不同浓度下诱导晶状体上皮细胞增殖和分化。fggf通过结合和激活细胞表面FGF受体（fgfr）引发细胞内反应。fgfr是膜结合酪氨酸激酶，激活后，激活导致特定细胞反应的特定信号通路。为了了解fgfr如何介导和调节晶状体细胞的不同反应，即细胞增殖和纤维分化，我们计划使用转基因小鼠晶状体中特异性表达的转基因fgfr来研究fgfr在正常晶状体发育中的作用。虽然已知正常发育的晶状体表达四种不同的FGF受体基因，但尚不清楚这些基因在晶状体细胞增殖和分化过程中所起的作用。此外，由于我们可以在体外重现特定的fgf诱导的晶状体细胞反应，我们将使用我们的晶状体外植体培养系统来剖析特定受体激活下游的信号通路，并将其与特定的细胞反应联系起来。通过识别控制正常晶状体发育所必需的细胞过程的分子和机制，我们可以更好地理解这些过程的破坏是如何导致白内障形成的。