Nuclear Receptor Function in Hypothalamic Development

DESCRIPTION (provided by applicant): The ventromedial nucleus of hypothalamus (VMH) has been implicated in regulating various behaviors, including metabolic homeostasis and reproduction. Despite its important roles in normal physiology, mechanisms of VMH development remain largely unknown. However, one nuclear receptor, Steroidogenic factor 1 (SF-1) has been previously shown to be required for VMH formation. In this application, I plan to determine how SF-1 orchestrates the formation of the VMH. To do this, I will first characterize molecular markers that are known to express in the hypothalamus to define the genetic pathway of SF-1. Next, I will identify a necessary promoter sequence to recapitulate SF-1 expression in vivo. This promoter region will then be used to express GFP or lacZ reporters that would allow us to mark and trace SF-1 expressing neurons during VMH development. This information is essential to identify neurons that are specified by SF-1 function. In addition, I will attempt to specifically ablate hypothalamic neurons that are dependent on SF-1 expression. This approach should elucidate physiological functions controlled by the VMH and will eliminate the confounding effects of early lethality exhibited in SF-1 null mice due to adrenal insufficiency. In summary, these studies will help to define pathways controlling VMH development and should provide insights into innate behaviors controlled by the neuroendocrine system.