My laboratory studies neural cell type specification, using mouse sensory system as a model. We focus on two groups of sensory neurons, somatic and visceral. Somatic sensory neurons are critical for sense of touch, pain, temperature and body position, while visceral sensory neurons control taste sensation and cardiorespiratory activities. Our goal is to understand how these distinct classes of sensory neurons are formed and make specific connections to the central targets. The approach we have been using is to conduct genome level survey to identify transcription factors (TFs) associated with sensory neurons, followed by genetic manipulation to study their functions. To this end, we have identified a TF expressed only in pain-related sensory neurons, and have demonstrated that this TF is required for expression of a subset of sensory receptors, including the hot and cold receptors and several sensory specific G-protein coupled receptors. This mouse line will be useful for screening for drugs that are targeted for specific types of pain. We have also been working on a TF that is expressed in neurons important for cardiorespiratory control.
In addition, we try to understand how distinct neurotransmitters are specified in the vertebrate brain. Glutamate and GABA are the predominant excitatory and inhibitory neurotransmitters, respectively. Disruption of homeostasis of excitation and inhibition is associated with many neurological disorders, such as epilepsy, schizophrenia, chronic pain, depression, and drug dependency. In the past years, we have found that two homeobox proteins, Lbx1 and Rnx, serve as the binary genetic switches that control the choices between GABA and glutamate transmitters. Lbx1 promotes GABA and suppresses glutamate neuron development, while Rnx does exactly opposite, promoting glutamate and suppressing GABA transmitter specification. Our studies provide a molecular basis of how excitatory and inhibitory neurons develop in a mutually exclusive manner, and provide a developmental basis for digital computational control of neuronal activities.