DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

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.

Publications

• Mizuguchi R, Kriks S, Cordes R, Gossler A, Ma Q, Goulding M.Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons.Nat Neurosci 2006 Jun;9(6):770-8.
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• Chen CL, Broom DC, Liu Y, de Nooij JC, Li Z, Cen C, Samad OA, Jessell TM, Woolf CJ, Ma Q.Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain.Neuron 2006 Feb 2;49(3):365-77.
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• Gray PA, Fu H, Luo P, Zhao Q, Yu J, Ferrari A, Tenzen T, Yuk DI, Tsung EF, Cai Z, Alberta JA, Cheng LP, Liu Y, Stenman JM, Valerius MT, Billings N, Kim HA, Greenberg ME, McMahon AP, Rowitch DH, Stiles CD, Ma Q.Mouse brain organization revealed through dir
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• Cheng L, Arata A, Mizuguchi R, Qian Y, Karunaratne A, Gray PA, Arata S, Shirasawa S, Bouchard M, Luo P, Chen CL, Busslinger M, Goulding M, Onimaru H, Ma Q.Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates.Na
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• Cheng L, Chen CL, Luo P, Tan M, Qiu M, Johnson R, Ma Q.Lmx1b, Pet-1, and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype.J Neurosci 2003 Nov 5;23(31):9961-7.
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• Qian Y, Shirasawa S, Chen CL, Cheng L, Ma Q.Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1.Genes Dev 2002 May 15;16(10):1220-33.
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• Qian Y, Fritzsch B, Shirasawa S, Chen CL, Choi Y, Ma Q.Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3.Genes Dev 2001 Oct 1;15(19):2533-45.
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