This proposal addresses fundamental issues regarding the formation of sensory maps in the mammalian brain. Experiments are proposed to sort out the role of factors that are Intrinsic to growing axons vs. of those derived from their environment in a model in vitro system. The rodent trigeminal system is a highly specialized sensory system; it is characterized by a specific arrangement of axonal and neuronal elements which are homeomorphic to the distribution of sensory receptors (around whiskers) on the snout. The patterned distribution of sensory receptors, or the sensory map, is conveyed to the brain by primary sensory neurons which reside in the trigeminal ganglion. In this proposal, embryonic trigeminal ganglia will be co-cultured with a variety of peripheral target tissue and central nervous system explants. This recently developed technical approach will be used to experimentally test the role of target- derived influences, such as cell and substrate adhesion molecules, glial organization within target tissues, possible positional cues embedded in the target, and of growth factors that are manufactured in the targets to reveal many unknown facets of axon-target interactions which lead to the formation of sensory maps in the brain. Understanding cellular and molecular mechanisms which underlie the formation of neural pathways and the spatial order within their tracts and terminal zones is a major endeavor in developmental neurobiology. Such knowledge has powerful implications for our ability to repair damage in specific sensory pathways of the brain.
