Resolving the origins of gonadotrophin-releasing homone neurons in the chick. (360G-Wellcome-078087_Z_05_Z)

This year-long pilot study aims to resolve finally the developmental origins of gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus and terminal nerve, which are critical for vertebrate fertility and reproduction. These neurons migrate into the brain along the olfactory nerves from the vicinity of the olfactory placodes, and a variety of fate-mapping and ablation studies have suggested they originate from the olfactory placodes themselves. However, a recent zebrafish fate-map has re-opened this debate by suggesting that cranial neural crest cells, which become intimately associated with the olfactory placodes, form at least some terminal nerve GnRH neurons, while the hypophyseal placode (which forms the anterior pituitary gland) forms hypothalamic GnRH neurons. The proposed series of quail-chick fate-mapping experiments, performed before neural crest cells reach the olfactory placodes, should settle the question of whether forebrain GnRH neurons in tetrapods are derived from neural crest cells, the hypophyseal placode or (as generally supposed) the olfactory placodes. This will resolve a long-standing debate and clarify our understanding of Kallmann's syndrome, in which GnRH neurons fail to reach the brain, resulting in hypogonadism. It will also provide an essential baseline for future experiments on the induction of GnRH neurons.