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The Journal of Neuroscience, March 21, 2007, 27(12):3078-3089; doi:10.1523/JNEUROSCI.3055-06.2007

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Development/Plasticity/Repair
Lhx6 Activity Is Required for the Normal Migration and Specification of Cortical Interneuron Subtypes

Petros Liodis,¹ Myrto Denaxa,¹ Marirena Grigoriou,¹ Cynthia Akufo-Addo,¹ Yuchio Yanagawa,² and Vassilis Pachnis¹

¹Division of Molecular Neurobiology, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom, and ²Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine and Solution-Oriented Research for Science and Technology, Maebashi 371-8511, Japan

Correspondence should be addressed to Vassilis Pachnis, Division of Molecular Neurobiology, Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Email: vpachni{at}nimr.mrc.ac.uk

The cerebral cortex contains two main neuronal cell populations, the excitatory glutamatergic (pyramidal) neurons and the inhibitory interneurons, which synthesize GABA and constitute 20–30% of all cortical neurons. In contrast to the mostly homogeneous population of projection neurons, cortical interneurons are characterized by remarkable morphological, molecular, and functional diversity. Among the markers that have been used to classify cortical interneurons are the calcium-binding proteins parvalbumin and calretinin and the neuropeptide somatostatin, which in rodents identify mostly nonoverlapping interneuron subpopulations. Pyramidal neurons are born during embryogenesis in the ventricular zone of the dorsal telencephalon, whereas cortical interneurons are generated in the subpallium and reach the cortex by tangential migration. On completion of tangential migration, cortical interneurons switch to a radial mode of migration and enter the cortical plate. Although the mechanisms that control the generation of interneuron diversity are currently unknown, it has been proposed that their site of origin in the ventral forebrain determines their specification into defined neurochemical subgroups. Here, we show that Lhx6, a gene induced in the medial ganglionic eminence and maintained in parvalbumin- and somatostatin-positive interneurons, is required for the specification of these neuronal subtypes in the neocortex and the hippocampus. We also show that Lhx6 activity is required for the normal tangential and radial migration of GABAergic interneurons in the cortex.

Key words: calretinin; forebrain; interneuron; Lhx6; LIM homeodomain; neocortex; parvalbumin; somatostatin

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Received July 19, 2006; revised Jan. 11, 2007; accepted Feb. 6, 2007.

Correspondence should be addressed to Vassilis Pachnis, Division of Molecular Neurobiology, Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Email: vpachni{at}nimr.mrc.ac.uk

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