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UNDERSTANDING THE GENETIC CODE BY WHICH CORTICAL INTERNEURONAL SUBCLASSES ARE SPECIFIED


Work by numerous groups over the past decade have revealed a large number of genes involved in the specification of the subpallial progenitor zones from which cortical interneurons arise. However the logic and timing by which specific cortical interneurons subtypes are specified remains unclear. Recently we have taken a first step to systematically determine all genes expressed within developing cortical interneurons. We have undertaken a genome-wide microarray analysis of cortical interneurons as they enter into the pallium (Batista-Brito et al., 2008). This analysis identified virtually all known transcription factors that have been implicated in cortical interneuronal development. In addition, we uncovered a large number of novel genes that appear to be involved in this process. We expect to further refine this analysis through a two pronged iterative analysis. First, we are beginning a large-scale effort to assemble Cre, CreER and FLPe driver lines for genetically fate mapping candidate transcription factors utilized in subsets of cortical interneuron precursors. We are also undertaking a null and conditional-null analysis of many of these genes to ascertain their contribution to the development of specific cortical interneuronal subtypes. In parallel, we are using a more fine-grained microarray analysis of wild type and conditionally mutant fate mapped interneurons to use iteratively with our wide scale screen to identify genes utilized in specific subset of cortical interneurons.


Related Publications

Butt, S., J., B., Fuccillo, M., Nery, S., Noctor, S., Kriegstein, A., Corbin, J., G. and Fishell, G. The Temporal and Spatial Origins of Cortical Interneurons predicts their Physiological Subtype. Neuron 2005 48, 591-604.

Miyoshi, G., Butt, S.J.B., Takebayashi, H. and Fishell, G. Physiologically distinct temporal cohorts of cortical interneurons arise from telencephalic Olig2-expressing precursors. Journal of Neuroscience, 2007, 27:7786 -7987.

Butt, S., J., Sousa, V.H., Fuccillo, M., Hjerling-Leffler, J., Miyoshi, G., Kimura, S. and Fishell, G. The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes. Neuron, 2008, 59: 722-732.

Batista-Brito, R., Rossignol,E., Hjerling-Leffler, J., Denaxa, M., Wegner, M., Lefebvre, V., Pachnis, V. and Fishell, G. The cell -intrinsic requirement of Sox6 for cortical interneuron development. Neuron, 2009, 63: 466-481.

Miyoshi, G., Hjerling-Leffler, J., Karayannis, T., Sousa, V.H., Butt, S.J.B., Battiste, J., Johnson, J.E., Machold, R.P. and Fishell, G. Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. Journal of Neuroscience, 2010, 30: 1582-1594.

Lee, S-H., Hjerling-Leffler, J., Zagha, E., Fishell, G. and Rudy, B. The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors. Journal of Neuroscience, 2010, 30: 16796-16808.

Tricoire, L., Pelkey, K.A., Daw, M.L., Miyoshi, G., Sousa, V.H., Miyoshi, G., Jefferies, B., Caulli, B., Fishell, G. and McBain, C.J. Common origins of hippocampal ivy and nitric oxide synthase expressing neurogliaform cells. Journal of Neuroscience, 2010, 30: 2165-2176.