CELL-MATRIX INTERACTIONS IN LIMB DEVELOPMENT

肢体发育中的细胞-基质相互作用

• 批准号: 2198911
• 负责人: BRYAN P TOOLE
• 金额: $ 70.98万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2198911
• 关键词: cell growth regulation; histogenesis; limbs; nonmammalian vertebrate embryology

The central theme of this proposal is the cellular and molecular events that lead to differentiation of most of the major tissues of the developing limb, namely cartilage, bone, tendon, muscle, and the vasculature. Project I will examine the role of a putative complex of hyaluronan, hyaluronan-binding protein and an integrin in regulating endothelial cell behavior, and the molecular nature of the protein components of this complex. Project II will continue to elucidate the specific regulatory components involved in cartilage hypertrophy, especially type X collagen, proteoglycans and other genes specifically expressed during hypertrophy. Project III will study the regulation of a critical step in maturation of collagen fibers during tendon development, also focussing on proteoglycan-collagen interactions and expression of genes at the time of tendon maturation. Project IV will further study translation-inhibitory RNAs in the regulation of muscle growth, and will also apply this concept to early differentiation events in the limb. The individual projects will employ a large variety of technical approaches to achieve their aims; a major integrating factor in the program is the sharing of the broad range of skills that have been mastered by the members of the program in order to facilitate progress in each project and to stimulate new experimental approaches. These studies will lead to a better understanding of morphogenesis and differentiation during limb development, and will provide a more informed basis for investigations of genetic and teratologically produced limb anomalies.

该提案的中心主题是细胞和分子事件 导致大多数主要组织的分化 发育中的肢体，即软骨、骨、肌腱、肌肉和 脉管系统。 项目我将研究一个假定的综合体的作用 乙酰透明质酸、乙酰透明质酸结合蛋白和整合素在调节中的作用 内皮细胞行为和蛋白质的分子性质 这个复合体的组成部分。 项目二将继续阐明 涉及软骨肥大的特定调节成分， 尤其是X型胶原蛋白、蛋白多糖等基因 肥大时表达。 项目三将研究监管 肌腱过程中胶原纤维成熟的关键步骤 开发，还关注蛋白聚糖-胶原蛋白相互作用和 肌腱成熟时基因的表达。 项目四将 进一步研究翻译抑制RNA在肌肉调节中的作用 生长，并将这一概念应用于早期分化事件 在肢体中。 各个项目将雇用各种各样的人员 实现其目标的技术方法；一个主要的整合因素 该计划的目的是分享广泛的技能 由计划成员掌握以促进进展 在每个项目中并激发新的实验方法。 这些 研究将有助于更好地理解形态发生和 肢体发育过程中的分化，并将提供更明智的信息 遗传和畸形肢体研究的基础 异常。