DEVELOPMENT AND MIGRATION OF LHRH NEURONS

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Neurons which synthesize luteinizing hormone-releasing hormone (LHRH) play a pivotal role in the control of vertebrate reproduction. A pattern of LHRH expression suggestive of migration of LHRH neurons from olfactory epithelium to brain has been found in mammals. This represents one of the few examples of neuronal migration from the periphery to the central nervous system. The failure of LHRH neurons to migrate into the CNS has been linked to a human disease, Kallman's syndrome. Our preliminary studies in chicks also suggest that LHRH neurons may migrate from the olfactory epithelium to the brain. Since the embryos of chicks are more accessible for perturbation experiments than mammalian embryos, the chick provides unique opportunities to study the origin, migration and function of LHRH neurons. To confirm that all encephalic LHRH neurons originate within the olfactory epithelium, we will ablate the olfactory epithelium early in development which we hypothesize will produce a chick without any LHRH neurons. In addition, we will transplant quail olfactory epithelium to chick embryos with ablated olfactory epitheliums which will permit labeling of all cells derived from the olfactory epithelium. In electron microscopic studies, we will examine interactions between LHRH neurons and their substratum in the three different terrains they traverse: olfactory epithelium, olfactory nerve and brain. As a number of authors have suggested that the glia ensheathing the olfactory nerve originate in the olfactory epithelium, we will label these cells with specific antibodies (1E8) and will determine the relationship between glial development and the development of the LHRH neurons. We have found that high levels of N-CAM expression are found within the developing olfactory system in the chick. We will use double-label immunocytochemistry to determine whether adhesion and/or extracellular matrix molecules are expressed at high levels at spatially and temporally restricted periods of chick development that correspond to the LHRH migration pathway. Finally, we will develop an in vitro explant slice culture system with the ultimate goal of directly testing whether particular adhesion or extracellular matrix molecules are involved in LHRH neuron migration.