The effects of extracellular matrix glycosaminoglycans on adhesion and histogenesis of neural retina cells

Graduation date: 1983Glycosaminoglycans, highly anionic long chains of repeating disaccharides,\ud are present in the extracellular matrix of almost all\ud vertebrate tissues. In addition to their structural role in adult\ud tissues, these molecules have been implicated as mediators of\ud important developmental processes such as cell migration, cell-cell\ud recognition and adhesion, and cytodifferentiation. The mechanism of\ud their action in affecting these processes probably involves an interaction\ud between the glycosaminoglycan and the cell surface. The work\ud reported here examines the nature and degree of specificity of the\ud interaction which occurs between cells of the developing neural\ud retina and the glycosaminoglycans found in retina extracellular matrix.\ud A study of retina cell behavior on collagen gels containing\ud glycosaminoglycan is presented in an appendix to this thesis, as are\ud studies related to the physical rather than biological nature of\ud the glycosaminoglycans. In the body of this thesis experiments are\ud described wherein neural retina cells from 10-day chick embryos were\ud tested for their ability to attach to Sepharose 4B beads which had\ud been derivatized with either chondroitin-6-sulfate or hyaluronic acid.\ud The cells were isolated by trypsin dissociation and were tested\ud directly or after preincubation in medium with or without either glycosaminoglycan.\ud Attachment of cells was inhibited when they had been\ud previously exposed to 10 mg/m1 chondroitin sulfate or 2.5 mg/ma\ud hyaluronic acid, regardless of the type of bead included in the culture.\ud By using freshly-dissociated cells to which chondroitin sulfate\ud was added simultaneously with the addition of either chondroitin\ud sulfate-derivatized or nonderivatized beads, cell attachment was\ud found to be inhibited at certain threshold concentrations which\ud differed for the two types of bead, being lower for the cells combined\ud with the chondroitin sulfate-derivatized beads. These results support\ud a model of cell-glycosaminoglycan interactions in which a close association\ud of exogenous glycosaminoglycan with the cell surface blocks\ud cell attachment to beads either by steric effects of the bulky sugars\ud or by masking cell adhesion sites