Gonadotropin-releasing hormone (GnRH) neurons, a population of neuroendocrine cells located in the brain, produce and secrete GnRH, a neurohormone essential for vertebrate reproduction. Unlike most neurons in the brain, GnRH neurons are born outside the central nervous system in the embryonic nose. From the nose, GnRH neurons migrate into the brain and target their axons to the median eminence of the hypothalamus for GnRH release. GnRH neuron development expemplifies key processes of neuronal development, namely differentiation, cell migration and axon targeting. Currently, developmental regulation of these key events in GnRH neurons is not well understood. In this proposal, I hypothesize that the fibroblast growth factor (FGF) signaling contributes to the formation of a functional GnRH neurosecretory system. I propose FGFs directly regulate the differentiation of GnRH neurons during discrete stages of GnRH neuronal development. In developing GnRH neurons, the role of FGF signaling and contributing receptors (FGFRs) will be identified. Critical stages of GnRH neuron development will be evaluated in mice to discern the functional contribution of FGF signaling in this important neuroendocrine system. ? ?
| Gill, John C; Tsai, Pei-San (2006) Expression of a dominant negative FGF receptor in developing GNRH1 neurons disrupts axon outgrowth and targeting to the median eminence. Biol Reprod 74:463-72 |
| Tsai, Pei-San; Gill, John C (2006) Mechanisms of disease: Insights into X-linked and autosomal-dominant Kallmann syndrome. Nat Clin Pract Endocrinol Metab 2:160-71 |
