Our long term objective is to gain a molecular understanding of morphogenetic processes in higher organisms by examining the differentiation of cartilage in the limb of the avian embryo. We will pursue these objectives by investigating the functional, structural, and immunochemical characteristics of proteoglycans synthesized by chondrocytes and by the mesenchymal cells of the limb from which the chondrocytes differentiated. We will also investigate the functional, structural and immunochemical characteristics of the link proteins which stabilize the proteoglycan aggregates of the extracellular matrix of cartilage. We will study the molecules themselves and also the mechanisms which regulate their synthesis. These studies will be performed on the limbs of genetically normal embryos as well as on the limbs of a number of mutant embryos whose limbs are abnormal due to a genetic lesion affecting the synthesis of extracellular matrix components of their cartilage. Not only are the mutants used to help us understand the developmental processes in normal embryos but they are also used as model systems for the study of hereditary diseases in general including in humans. Attempts will be made to correct the expression of one of the hereditary defects which we are studying.