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The Journal of Neuroscience, October 10, 2007, 27(41):10935-10946; doi:10.1523/JNEUROSCI.1629-07.2007

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Development/Plasticity/Repair
Spatial Genetic Patterning of the Embryonic Neuroepithelium Generates GABAergic Interneuron Diversity in the Adult Cortex

Matthew Fogarty,¹ Matthew Grist,¹ Diego Gelman,² Oscar Marín,² Vassilis Pachnis,³ and Nicoletta Kessaris¹

¹Wolfson Institute for Biomedical Research and Department of Biology, University College London, London WC1E 6AE, United Kingdom, ²Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas/Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Alicante, Spain, and ³Division of Molecular Neurobiology, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom

Correspondence should be addressed to Nicoletta Kessaris, Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London WC1E 6AE, UK. Email: n.tekki-kessaris{at}ucl.ac.uk

Cortical pyramidal cells are generated from pallial neuroepithelial precursors, whereas GABAergic interneurons originate in subpallial germinal zones and migrate tangentially to reach the cortex. Using Cre–lox technology in transgenic mice and a series of molecular markers that subdivide the subpallial neuroepithelium into small domains, we fate-map precursor pools and identify interneurons generated from each domain. Cortical interneurons expressing calbindin, parvalbumin, and somatostatin are generated exclusively from Lhx6 (Lim homeobox 6)-expressing precursors in the medial ganglionic eminence (MGE). Martinotti cells that coexpress calretinin and somatostatin are generated from the dorsal region of the MGE neuroepithelium that expresses Nkx6.2 (NK2 transcription factor-related 6.2). Most neuropeptide Y-expressing cells and all bipolar calretinin-expressing interneurons are generated outside the MGE, from the germinal zones of the lateral/caudal ganglionic eminences that express Gsh2 (genomic screened homeobox 2). Our data demonstrate that subpallial neuroepithelial domains defined by expression of genetic determinants generate distinct interneuron subtypes, thereby contributing to the generation of cortical interneuron heterogeneity observed in the adult cortex.

Key words: cell fate; cortex; Cre-transgenic; development; GABAergic neuron; interneurons

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Received April 11, 2007; revised Aug. 2, 2007; accepted Aug. 24, 2007.

Correspondence should be addressed to Nicoletta Kessaris, Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London WC1E 6AE, UK. Email: n.tekki-kessaris{at}ucl.ac.uk

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