Serine Proteases and Their Inhibitors Affect the Rate of GnRH Neuronal Migration in the Embryonic Chick Model: A Thesis Proposal

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Development in an organism is a highly complex task that requires a specific sequence for proper function. One of these tasks is neuronal migration and the extracellular cues that help to guide neurons to their appropriate locations. If neurons do not migrate to their appropriate locations, then there are abnormal neural connections, which can result in neuronal migration disorders (NMD). It has been shown that the inhibition and stimulation of migration may be balanced due to effects of serine protease inhibitors and serine proteases. Serine proteases and their inhibitors can alter the various chemoattraction-signaling cues and thereby modulate neuronal migratory processes. Furthermore, there exists a delicate balance between serine proteases and their inhibitors to modulate migration of neurons within development. Thus, by understanding how the balance of serine protease and serine protease inhibitor activity works, one can further understand how these changes affect neuronal migration in development. Experiments to test in vivo neuronal migration of chick GnRH neurons during embryogenesis were investigated to elucidate the role these proteins play in migration. Protein coated beads were inserted and GnRH levels measured to control. Such experimentation is crucial, as these studies are the first to explore the role of proteases in neural migration in an in vivo model. These findings indicate that the ability to initiate migration lies inherently within the neuron itself such that changes of the extracellular matrix composition are irrelevant in the initial timing. Neurons entering the CNS earlier in trypsin-treated embryos indicates continuous movement may be a cell autonomous event with trypsin-induced proteolysis. In other words, the ability of GnRH neurons to migrate across glial boundaries and through the brain to its target site is independent of further maturation of the neuron or the brain. Taken together, this study can provide knowledge regarding these proteins and their relation to development. This knowledge can potentially lead to therapies that can provide ameliorative care for patients suffering with NMD.