Inducing sterility in farmed fish by disrupting the development of the GnRH System.

Hypothalamic gonadotropinreleasing hormone (GnRH1) is the key hormone in the control of gametogenesis and gonadal growth in vertebrates. Developmentally, hypothalamic GnRHproducing neurons originate from the olfactory placode, migrate along olfactory axons into the forebrain, and continue to the preoptic area and hypothalamus where they function to stimulate gonadotropin secretion from the pituitary gland. An appropriate location of GnRH neurons within the hypothalamus is necessary for normal reproductive function in the adult; abnormal migration and targeting of GnRH neurons during embryogenesis results in hypogonadism and infertility. The developmental migration of GnRH neurons and axonal pathfinding in mammals are modulated by a plethora of factors, including receptors, secreted molecules, adhesion molecules, etc. Yet the exact mechanism that controls these developmental events is still unknown. We investigated these developmental events and the underlying mechanisms using a transgenic zebrafish model, Tg(gnrh1: EGFP), in which GnRH1 neurons and axons are fluorescently labeled. The role of factors that potentially affect the development of this system was investigated by testing the effect of their knockdown and mutation on the development of the GnRH1 system. In addition, their localization in relation to GnRH1 was described during development. These studies are expected to generate the scientific foundation that will lead to developing innovative technologies, based on the disruption of the early establishment of the GnRH system, for inducing sterility in farmed fish, which is highly desirable for economical and environmental reasons.