CELLULAR RECOGNITION AND CARDIAC MORPHOGENESIS

心脏发育过程中细胞发生的巨大变化是 几种形态发生因子的表达和相互作用的结果 因素 在心脏发育的关键时期，如循环， 分隔、小梁形成和瓣膜形成，这些因素发挥了 在决定发展中国家的形式和功能方面的重要作用 心 心脏发育所需的基本事件包括 细胞外基质（ECM）成分的表达、排列和 ECM的重塑，ECM与细胞成分的附着，以及ECM与细胞成分的结合。 细胞的形成：细胞接触。 拟议的调查将集中在 ECM成分与特定细胞表面受体之间的相互作用 心脏细胞成分的分化。 另外还 将检查：1）整合素和钙粘蛋白在不同的细胞周期中的表达。 心脏发育的各个阶段; 2）基底膜的表达 心肌细胞发育过程中的成分及其可能的作用 心脏的分化; 3）生长的作用 因子/细胞因子对整合素、钙粘蛋白和 心脏发育过程中的胶原酶。 几种实验方法 将用于分析这些具体目标，包括：A）三维 胶原凝胶培养以检查生长因子/细胞因子对 ECM成分、其特异性受体和 金属蛋白酶; B）细胞迁移，细胞与聚集体的相互作用 在旋转培养中形成，以及细胞：ECM粘附测定，以确定 潜在的调节成分的作用; C）显微注射整个 胚胎培养物和单个细胞，以确定调节 在特定的发展阶段的组成部分; D）形态和 特异性调节因子免疫定位的形态计量学分析 在发育的关键阶段的成分及其受体;以及 E）分析调控基因的生物化学和分子表达， 胶原凝胶中的成分，胚胎培养与体内培养相比 发展 这些实验方法将允许分析 与正常心脏相关的形态发生事件的调节 发展和提供有关机制的基本数据， 先天性心脏病

The dramatic cellular changes that take place during heart development are the result of the expression and interaction of several morphogenetic factors. At critical times in heart development, such as looping, septation, trabeculation, and valve formation, these factors play a significant role in determining the form and function of the developing heart. Fundamental events necessary for heart development include the expression of extracellular matrix (ECM) components, arrangement and remodeling of ECM, attachment of the ECM to cellular components, and the formation of cell:cell contacts. The proposed investigations will focus on the interaction between ECM components and specific cell surface receptors of the differentiating cellular components of the heart. Specifically we will examine: 1) the expression of integrins and cadherins at different stages of heart development; 2) the expression of basement membrane components during development by cardiac myocytes and their possible role in differentiation of the heart; and 3) the role of growth factors/cytokines on the regulation of integrins, cadherins and collagenases during cardiac development. Several experimental approaches will be used to analyze these specific aims including: A) 3-dimensional collagen gel cultures to examine the effects of growth factors/cytokines on expression of ECM components, their specific receptors and metalloproteases; B) cell migration, cell-cell interaction with aggregate formation in rotation culture, and cell:ECM adhesion assays to determine the role of potential regulatory components; C) microinjection of whole embryo cultures and individual cells to determine the effects of regulatory components at specific stages of development; D) morphological and morphometric analysis of immunolocalization of specific regulatory components and their receptors during critical stages of development; and E) analysis of the biochemical and molecular expression of regulatory components in collagen gels, embryo culture compared to in vivo development. These experimental approaches will allow for the analysis of the regulation of the morphogenetic events associated with normal heart development and provide essential data on the mechanisms involved in congenital heart defects.