Role Of ECM In Cell Differentiation And Embryogenesis

细胞外基质在胚胎发生和组织修复中起着重要的作用。通过使用纯化组分的体外研究，我们对细胞如何粘附、迁移、增殖和分化以响应组织和细胞特异性基质分子有了更好的了解。我们发现基底膜，即所有上皮细胞和内皮细胞以及神经细胞周围的细胞外基质，在体外促进细胞分化。在基底膜上培养时，内皮细胞形成带有管腔的毛细血管样结构，软骨细胞形成软骨，唾液细胞形成腺体等。我们的目标是确定参与这一过程的分子和细胞事件。我们的方法是(1)鉴定具有生物活性的基质成分，与细胞粘附、迁移、增殖和分化有关；(2)用合成肽定位基质成分上的活性位点；(3)鉴定和表征细胞受体；(4)了解参与生物反应的细胞内事件；(5)鉴定由细胞外基质诱导的基因。我们在几个体外模型系统中工作，包括原代和已建立的肿瘤细胞、内皮细胞和唾液腺和细胞。我们已经在体外和体内使用内皮细胞试管实验来确定在发育、修复和疾病中调节血管形成的分子。我们的目标是发现具有生理和临床相关性的新的血管生成调节因子。唾液腺细胞和体外发育中的腺体已被用来确定对腺体发育和功能重要的因素。我们的目标是了解细胞外基质如何调节组织形成、修复和某些病理过程。我们希望开发治疗和诊断试剂。

The extracellular matrix has been found to be important in embryogenesis and in tissue repair. From in vitro studies using purified components, a better understanding of how cells adhere, migrate, proliferate, and differentiate in response to tissue and cell- specific matrix molecules has been established. We have found that the basement membrane, the extracellular matrix which underlies all epithelial cells and endothelial cells and surrounds nerve cells, promotes cell differentiation in vitro. When cultured on basement membrane, endothelial cells form capillary-like structures with a lumen, chondrocytes form cartilage, salivary cells form glands, etc. Our goal is to define the molecular and cellular events involved in this process. Our approach has been (1) to identify the biologically active matrix components, with respect to cell adhesion, migration, proliferation and differentiation, (2) localize active sites on the matrix component with synthetic peptides, (3) identify and characterize cellular receptors, (4) gain an understanding of the intracellular events involved in the biological response, and (5) identify genes induced by the extracellular matrix. We work in several in vitro model systems including primary and established tumor cells, endothelial cells, and salivary glands and cells. We have used the endothelial cell tube assays in vitro and in vivo angiogenesis assays to define molecules which regulate vessel formation in development, repair, and disease. Our goal is to discover new angiogenic regulators that have physiological and clinical relevance. Salivary gland cells and developing glands in vitro have been used to define factors important to gland development and function. Our goal is to understand how the extracellular matrix regulates tissue formation, repair, and certain pathological processes. We hope to develop both therapeutic and diagnostic agents.