Axonal Navigation in the Developing Visual System

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9870784 HALFTER In the developing nervous system, axons must often establish contact with specific targets by complicated routes. Despite considerable progress in understanding how axons make navigational choices, the mechanisms and molecular components that can precisely account for the specificity of axonal wiring are still largely unknown. In the current project, Dr. Halfter plans to continue his research on the question of how optic axons from the eye are guided to grow towards the optic disc and cross to the other side of the brain at the optic chiasm, and from there, to form synapses with the correct parts of the tectum, their initial target in the brain. Previous work in Dr. Halfter's laboratory has shown that membrane and extracellular matrix proteins on cells in the path of growing retinal axons are likely to act as intermediary targets. They have recently isolated an unknown cell-surface protein called the ID10 antigen which is a candidate guidance molecule. The first goal of the new research will be to molecularly identify this protein and characterize its function in axon guidance. A second aim of this research is to investigate how gradients of substances that either attract or repel growing axons can precisely guide axonal growth. For this aim, Dr. Halfter has developed an in vitro system for producing gradients of suspected attractive or repellent molecules. The third part of this project will take a molecular approach to identifying new candidate molecules for axonal guidance by their differential expression in retinal ganglion cells from different locations in the eye. These studies will contribute to a general understanding of the mechanisms of axon guidance, and provide new methodology for assaying the effects of candidate molecules.