Research Description
The central dogma of vertebrate reproductive endocrinology is that reproduction consists of three tiers of regulation. At the top is the brain that interprets environmental and physiological cues and secretes a critical neurohormone called gonadotropin-releasing hormone (GnRH) when the environmental and physiological conditions are conducive to reproduction. At the middle is the pituitary gland that secretes two hormones, collectively called gonadotropins, when stimulated by GnRH from the brain. At the bottom are the gonads, the ovaries and testes. They grow, produce gametes and secrete steroid hormones such as testosterone and estrogen in response to gonadotropins from the pituitary gland. These three tiers of regulation, collectively called the hypothalamic-pituitary-gonadal (HPG) axis, form the basis of vertebrate reproductive regulation. Defects in any of these three regulatory levels will lead to reproductive abnormality and sterility. My current research program aims to investigate the following three questions:
(1) how neurons that produce and secrete GnRH develop and mature under the guidance of signaling factors called fibroblast growth factors (FGFs),
(2) how an ancient molecule like GnRH evolved functionally and structurally over time,
(3) how dysregulation of FGF signaling during development can lead to the malformation of the endocrine hypothalamus, thereby deleteriously affecting reproductive and non-reproductive mental functions.
GnRH neurons have an unusual embryonic origin. They arise in the nasal region and migrate into the brain during development. Once in the brain, GnRH neurons target their axons to the external zone of median eminence to release GnRH into the hypothalamic-pituitary portal circulation. We are interested in how neurotrophic factors, primarily fibroblast growth factors (FGFs), guide the development of these neurons.