lec09_lena_cheng

lec09_lena_cheng - Tlx3 and Tlx1 are post-mitotic selector...

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Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates L. Cheng, A. Arata, R. Mizuguchi, Y. Qian, A. Karunaratne, P.A. Gray, S. Arata, S. Shirasawa, M. Bouchard, P. Luo, C.-L. Chen, M. Busslinger, M. Goulding, H. Onimaru, and Q. Ma by Lena Khibnik 3/8/05
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Central Questions • Molecular specification of neurotransmitter types in different neuronal populations • Choice of excitatory vs. inhibitory fate • Is there a “master switch” that makes a cell fate choice?
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Exctation vs. Inhibition • Glutamate is the major excitatory neurotrasmitter • GABA is the major inhibitory neurotransmitter • Glu and GABA rarely coexist in one neuron Two Puzzles: • Glu is expressed everywhere (what is Glu?) • GABA can be synthesized from Glu in a single step (via GAD)
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A bit about the system… Embryonic Dorsal Spinal Cord - neurogenesis has been extensively characterized - well characterized neuronal populations Existence of distinct excitatory and inhibitory pupulation Both types derive from a specific domain in the ventricular zone and migrate to superficial lamina in the dorsal horn Photo removed for copyright reasons. Spinal cord cross-section, highlighting two dorsal horn regions.
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Methods • Embryonic mouse and chick spinal cord • Detection of gene and protein expression and co-localization via in situ hybridization and immuno staining techniques • Genetic manipulation (knockouts; overexpression) • Electrophysiology (whole cell patch)
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How do you tell glutamatergic neuron from GABAergic? Glutamatergic neuron specific expression: VLUT2 = Glu transporter GABAergic neuron specific expression: GAD = glutamic acid decarboxylase Viaat = GABA transporter Source: Cheng, L., et al. "Tlx3 and Tlx1 are Post - Mitotic Selector Genes Determining Glutamatergic over GABAergic Cell Fates." Nature Neuroscience 7 (2004): 510- 517. Courtesy of the authors. Used with permission.
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• Central question: what’s the “switch” that decides cell fate for glutamatergic vs. GABAergic neurons? - Transcription factors are usually involved in cell
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lec09_lena_cheng - Tlx3 and Tlx1 are post-mitotic selector...

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