No coin nor oath required. For personal study only.
The migration of the hypophysiotropic GnRH (GnRH-I) neurons during early development is a crucial step in establishing a normally functioning reproductive system in all vertebrates. These neurons derive from progenitor cells in the olfactory placode and subsequently migrate to their final position in the ventral forebrain, where they mediate hypophysiotropic control over Lh. We use zebrafish as a model to investigate the path and the factors that mediate the migration of the GnRH-I neurons during early development. A transgenic line of zebrafish, in which GnRH-I neurons specifically express a reporter gene (GFP) has been developed in our lab. This was achieved by integrating a GnRH-I promoter/GFP reporter transgene into the zebrafish genome. The resulting transgenic line allows us to track the route of the GnRH-I neuronal migration in real time and in vivo. We have used this line to conduct time lapse imaging to ascertain the exact migrational path and the final position in the ventral forebrain of the GnRH-I neurons. We are also studying the role of various factors in mediating the migration process of the GnRH-I neurons. Our focus is on the role of the chemoattractant netrin-1a and its receptors (DCC and UNC5B) in guiding the GnRH-I neurons, especially in the later stages of migration when the GnRH-I neurons cross the cribriform plate and turn caudoventrally. To study this, we over-express netrin-1a in the GnRH-I neurons by using a GnRH-I promoter/netrin-1a transgene, thus creating an abnormal gradient of this chemoattractant in immediate proximity to the GnRH-I neurons. We expect that this abnormal distribution of netrin will disrupt the normal migration of the GnRH-I neurons.
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