Numerous peptide hormones are involved in tissue development and differentiation.
The aim of this proposal is to establish the role of retina-derived growth factor (RDGF) in the development and differentiation of neural tissue. RDGF is an anionic peptide hormone that has been purified from bovine retina by taking advantage of its unusually high affinity for heparin. RDGF is a potent mitogen for endothelial cells and its mitogenic activity is potentiated by exogenous heparin. The apparently specific association of RDGF with heparin has led to the suggestion that the factor may be capable of forming stable associations with the basement membrane in vivo. We have discovered that RDGF stimulates PC12 cells (a useful model for the study of neural differentiation) to extend neurites (long neuronal processes similar to axons or dendrites). This stimulation is not inhibited by antisera to nerve growth factor and is potentiated by heparin. Thus, RDGF may define a new class of neuronal growth factors, capable of regulating differentiation in association with extracellular matrix.
The specific aims of this grant are: (1) to determine what types of neural cells respond to RDGF by surveying five different classes of cells in vitro, (2) to investigate which other differentiated functions of neural cells are regulated by RDGF and (3) to examine the ability of basement membrane-associated glycosaminoglycans and glycoproteins to influence the action of RDGF. These experiments will help to establish the nature of the regulatory pathways controlled by RDGF and help to establish the relationship of RDGF to other regulators of neural differentiation. Our long-term goal is to establish the physiological role of RDGF. We speculate that RDGF may be functional in normal developmental processes such as the regulation of patterns of innervation and vascularization and the response of vascular and neural tissue to injury as well as in thye etiology of various neural pathologies.
| Damon, D H; D'Amore, P A; Wagner, J A (1990) Nerve growth factor and fibroblast growth factor regulate neurite outgrowth and gene expression in PC12 cells via both protein kinase C- and cAMP-independent mechanisms. J Cell Biol 110:1333-9 |
| Damon, D H; Lobb, R R; D'Amore, P A et al. (1989) Heparin potentiates the action of acidic fibroblast growth factor by prolonging its biological half-life. J Cell Physiol 138:221-6 |
| Damon, D H; D'Amore, P A; Wagner, J A (1988) Sulfated glycosaminoglycans modify growth factor-induced neurite outgrowth in PC12 cells. J Cell Physiol 135:293-300 |
| Wagner, J A; D'Amore, P A (1986) Neurite outgrowth induced by an endothelial cell mitogen isolated from retina. J Cell Biol 103:1363-7 |
