Cell-cell recognition controls cell behaviors essential to orderly embryogenesis (division, motility, adhesion, differentiation). Loss of these controls is also implicated in neoplastic transformation and metastasis. Our goal is to describe the molecular mechanism of cell-cell recognition and how recognition controls cell behavior. Recognition is initiated when receptors on one cell bind to specific ligands on an apposing cell, triggering the appropriate response. The most complex examples of such recognition occur in the development nervous system, where each neuron must seek its proper target and initiate synapse formation.
Our aim i s to define the neuronal surface molecules which act as recognition markers during development. Cell surface complex carbohydrates (and complementary receptors on apposing cells) may constitute such markers. Therefore, we will study the role of a major class of neuronal cell surface glycoconjugates, gangliosides, in neuronal recognition. 1. Ganglioside-specific neuronal recognition and adhesion. Immobilized gangliosides support specific adhesion of cells dissociated from the embryonic chick neural retina. We propose to study the cellular and carbohydrate structural specificity of this adhesion. We will use cell separation techniques to test whether ganglioside recognition is cell type or positionally specific. Carbohydrate structural specificity will be probed using ganglioside derivatives as inhibitors of ganglioside-directed cell adhesion. We will complement these studies using our method for detecting cell adhesion directly to gangliosides separated on thin layer chromatography plates, allowing us to detect minor endogenous gangliosides as potential cell recognition markers. 2. Neuronal cell surface ganglioside receptors. Recent studies suggest the existence of specific cell surface ganglioside receptors. Detection of such receptors has been hampered by non-specific ganglioside binding to biological membranes. Therefore, we will synthesize multivalent hydrophilic ganglioside ligands which may provide the high affinity and low non-specific binding necessary to detect and characterize such receptors on brain membranes or on intact embryonic neurons. Success in finding high affinity, saturable, specific ganglioside receptors in these preparations will lead to further characterization of their binding properties, distribution and biochemistry.
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