Netrins Creating Divergent Axon Morphologies

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DESCRIPTION (provided by applicant): During nervous system development, axons must grow and make proper connections with their targets within the body. In recent years, the discovery of numerous molecules that regulate this process has allowed us to make great strides in understanding how axons find their targets. Surprisingly, many of the molecules that guide axonal growth cones are conserved amongst extremely divergent organisms. For example, Netrin proteins regulate growth of axons toward the midline in a wide variety of organisms, from fruit flies to mice. To date, research has mainly concentrated on the similarities in axon guidance amongst organisms. Such discoveries, while fascinating, have failed to explain how different neural network patterns have arisen in divergent organisms. This investigation aims to examine the molecular mechanisms underlying the creation of novel axonal morphologies. The specific aims of this investigation are: (1) to clone the netrin genes from Artemia franciscana and Parhyale hawaiensis, two crustaceans with extremely different axonal morphologies, (2) to analyze the expression patterns of these genes in relation to growing axons during Artemia and Parhyale development, and (3) to compare these expression patterns to those found in Drosophila melanogaster, a model organism in which the function of netrin genes is well documented. This work, particularly the analysis of Artemia, whose axons fail to grow toward the midline, will likely improve the basic understanding of how axonal guidance molecules can be used to create novel neural circuitry patterns. This could lead to a better understanding of how the complex neural circuitry patterns found in humans have arisen. Understanding the basic mechanisms that are used to create complex neural networks may someday enable us to recreate such complex networks in patients suffering from neural traumas.