MECHANISMS OF LENS FIBER DIFFERENTIATION

这些研究测试了几个新的假设， 鸡透镜纤维终末分化与生长的关系 因子、有丝分裂抑制和细胞-细胞相互作用。 以来 已知多种生长因子影响透镜的不同方面 细胞行为，相关生长因子受体及其 相关的信号转导机制最初将被编译， 有丝分裂后的上皮细胞和纤维细胞。 这些观察结果 将检验不同生长因子相关机制的假设， 表征透镜纤维发育的可识别阶段。 此外，本发明还提供了一种方法， 这些观察结果可用作评估 所有后续细胞培养操作对 纤维状性状的积累。 下一个主要假设是 测试的是，在终末期的初始阶段期间抑制有丝分裂 分化受细胞表面受体的主动调节。 三 体外模型将检查细胞内蛋白激酶的作用， 细胞外基质相互作用和细胞粘附糖蛋白 维持有丝分裂撤退，因为细胞-细胞相互作用增加， 聚集的细胞生长。 这些模型还将用于测试 假设，在有丝分裂抑制的细胞中， 生长因子的刺激可以使人更全面地了解 差异化特征 最后一个需要检验的主要假设是， 透镜纤维的发育能够受到内源性 生长因子或其受体的产生。 监测 文化中的特定差异事件，除了以前的 提到的生长因子机制，将包括更传统的和 新增原创标准。 完善的标准包括 蛋白质与DNA比率增加，核固缩和DNA片段化， 特定晶体蛋白的持续合成， 高水平的缝隙连接蛋白。 一种新的透镜光纤量规 分化需要积累，磷酸化， 49 kD细胞骨架蛋白的不溶解。 这不仅是 受受体介导机制影响的标记物，但它作为一种 纤维开发的可靠终点。 透镜的附加标记 纤维末端的分化是相对丰度 细胞膜中的NCAM。 这些研究将更全面地界定 透镜中的差异是受控的，并且可以提供对以下方面的新见解： 白内障发病的其他更基本的原因。

These studies test several novel hypotheses concerning the control of terminal differentiation in chick lens fibers with respect to growth factors, inhibition of mitosis and cell-cell interactions. Since multiple growth factors are known to influence diverse aspects of lens cell behavior, a profile of relevant growth factor receptors and their associated signal transduction mechanisms will initially be compiled for both post-mitotic epithelial cells and fiber cells. These observations will test the hypothesis that distinct growth factor related mechanisms characterize recognizable stages of lens fiber development. In addition, these observations can be utilized as new criteria for assessing the effectiveness of all subsequent cell culture manipulations on the accumulation of fiber-like traits. The next major hypothesis to be tested is that inhibition of mitosis during initial stages of terminal differentiation is actively regulated by cell surface receptors. Three in vitro models will examine the role of intracellular protein kinases, extracellular matrix interactions and cell adhesion glycoproteins in maintaining mitotic withdrawal as cell-cell interactions increase during aggregated cell growth. These models will also be utilized to test the hypothesis that, in mitotically inhibited cells, sequential or combined growth factor stimulation elicits a more complete profile of differentiated traits. The final major hypothesis to be tested is that lens fiber development is capable of being regulated by the endogenous production of growth factors or their receptors. The monitoring of differentiation-specific events in culture, aside from the previously mentioned growth factor mechanisms, will include more traditional and additional original criteria. Well established criteria include an increased protein to DNA ratio, nuclear pyknosis and DNA fragmentation, the persistent synthesis of specific crystallins, and the accumulation to high levels of gap junction proteins. A new gauge of lens fiber differentiation entails the accumulation, phosphorylation, and insolubilization of a 49 kD cytoskeletal protein. Not only is this marker affected by receptor-mediated mechanisms, but it serves as a reliable endpoint for fiber development. An additional marker of lens fiber terminal differentiation to be examined is the relative abundance of NCAM in cell membranes. These studies will more fully define how differentiation in the lens is controlled and may lend fresh insight into additional, more fundamental causes of cataract development.