Role of Primary Cilia in Metabolic State Sensing in Hypothalamic Neurons

The hypothalamus is a region of the brain that contains nerve cells (neurons) that regulate food intake. Alterations in the function of these cells can lead to obesity1. Hypothalamic neurons may sense metabolic signals in part through specialized sensory structures called primary cilia, which contain receptors that respond to hormones, nutrients, and drugs that regulate appetite2. Identifying the proteins expressed in primary cilia of hypothalamic neurons could facilitate the development of anti-obesity drugs or drug combinations. To identify ciliary receptors, I will take advantage of recent methods to generate human hypothalamic and other neuron types in culture from stem cells. In these cells I will target a protein to cilia that labels other proteins and allows them to be purified and identified. I will then experimentally activate or inactivate these proteins in cilia to study how they regulate neuronal activity.