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First published online 13 March 2008
doi: 10.1242/dev.015123

Development 135, 1559-1567 (2008)
Published by The Company of Biologists 2008
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NKX2.1 specifies cortical interneuron fate by activating Lhx6

Tonggong Du, Qing Xu, Polloneal J. Ocbina and Stewart A. Anderson*

Department of Psychiatry, and Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 1300 York Avenue, Box 244, New York, NY 10021, USA.

* Author for correspondence (e-mail: SAA2007{at}med.cornell.edu)

Accepted 2 February 2008

In the ventral telencephalon, the medial ganglionic eminence (MGE) is a major source of cortical interneurons. Expression of the transcription factor NKX2.1 in the MGE is required for the specification of two major subgroups of cortical interneurons - those that express parvalbumin (PV) or somatostatin (SST) - but direct targets of NKX2.1 remain to be established. We find that electroporation of Nkx2.1 cDNA into the ventral telencephalon of slice cultures from Nkx2.1-/- mouse embryos, followed by transplantation into neonatal cortex to permit postnatal analysis of their fate, rescues the loss of PV- and SST-expressing cells. The LIM-homeobox gene Lhx6 is induced by this rescue experiment, and gain- and loss-of-function studies suggest that Lhx6 is necessary and sufficient to rescue these and other interneuron phenotypes in cells transplanted from Nkx2.1-/- slices. Finally, NKX2.1 protein binds a highly conserved sequence in the Lhx6 promoter, and this sequence appears to mediate the direct activation of Lhx6 by NKX2.1. The slice transfection and transplantation methods employed here are beginning to uncover embryonic mechanisms for specifying neuronal fates that only become definable postnatally.

Key words: Cell fate determination, GABA, Medial ganglionic eminence, Nkx2.1, Parvalbumin, Somatostatin, Mouse






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