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.

白内障是眼镜镜的透明度的丧失，是世界失明的主要原因。白内障的最终治愈取决于对正常和白内障晶状体中基本分子过程的更好理解。我们的研究集中在确定控制镜头形成和维持的分子。生长因子是细胞行为的重要调节剂，我们的研究提供了令人信服的证据，表明FGF生长因子家族的成员通过影响晶状体细胞增殖和分化而在晶状体发育生物学中起关键作用。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的增殖和分化。 FGF与结合并激活细胞表面FGF受体（FGFR）时会引起细胞内反应。 FGFR是膜结合的酪氨酸激酶，激活后激活特定的信号传导途径，导致特定的细胞反应。为了了解FGF如何介导和调节晶状体细胞中的不同反应，即细胞增殖和纤维分化，我们计划使用遗传改变的FGFR来检查FGFR在正常晶状体发育中的作用，这些FGFR在转基因小鼠的透镜中特异性表达。虽然众所周知，四个不同的FGF受体基因是通过正常发育的晶状体表达的，但尚不清楚这些在晶状体细胞增殖和分化过程中的作用是什么作用。此外，由于我们可以在体外重现特定的FGF诱导的透镜细胞反应，因此我们将使用透镜外植体培养系统从特定受体激活中剖析下游的信号传导途径，并将其与特定的细胞反应相关。通过确定控制正常晶状体发育必不可少的细胞过程的分子和机制，我们可以更好地了解这些过程的破坏如何导致白内障形成。