This program-project consists of studies aimed at elucidation of certain aspects of the etiology of mental retardation and developmental disabilities. Studies will be conducted on the mechanisms of biosynthesis and control of the glycosaminoglycans and their protein complexes. Additional investigations are concerned with the mechanisms by which limb bud mesenchyme differentiates to cartilage. An attempt will be made to isolate the mRNA for the specific core protein of chondroitin sulfate proteoglycan and to determine the control of its synthesis. Using immunofluorescence, individual cells will be examined for synthesis of the core protein and Type II collagen. Studies on differentiation are also concerned with the change in the genome that occur in the course of differentiation. A number of human heritable diseases are due to deficiency of enzymes responsible for the degradation of glycominoglycans, glycosphingolipids and glycoproteins. Studies will be carried out to further characterize the nature of the enzyme defects with an aim toward improving methods of diagnosis, prevention and possibly treatment. Other projects involve the use of cultures of cells of neural origin to elucidate the mechanism and control of biosynthesis of glycosphingolipids with special reference to cerebroside sulfate. Coordinated with these studies will be investigations of the role of these substances in binding of enkephalins and opiates as well as the role of enkephalins in regulating synthesis of the glycosphingolipids.