Our goal is to develop a comprehensive map of the complex gene regulatory networks that direct cell-fate specification and assembly of neuro-circuits. Our major model systems include the spinal cord, which consists of distinct classes of neurons to assemble motor and sensory circuits, and the arcuate nucleus of the hypothalamus, which forms a core neuro-circuitry that mediates actions of peripheral adiposity signals, leptin and insulin, for energy balance. To achieve our goals, we dissect multiple layers of gene regulatory steps that render neuronal cell-fate specification, taking the following steps: to define transcription complexes specifying each neuronal population, to identify their downstream effector genes conferring unique cell-identity, to understand the epigenetic strategy orchestrating timely changes on gene transcription, to uncover the molecular mechanism by which the peripheral cues modulate neuronal gene expression, and to generate specific neuronal subtypes from stem cells by applying the developmental gene regulatory strategy that we define. We are employing combined approaches of mouse genetics and chick embryology to take advantage of their complementary strengths as experimental systems. In addition, we are utilizing embryonic stem cells extensively and biochemical and molecular methods to dissect the development of spinal and hypothalamic neurons.