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Neuron. 2013 Jan 9;77(1):83-98. doi: 10.1016/j.neuron.2012.11.035.

Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons.

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1
Department of Psychiatry, Neuroscience Program, and the Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco (UCSF), San Francisco, CA 94158-2324, USA.

Abstract

Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB, and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform toward a subtype of GABAergic striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome).

PMID:
23312518
PMCID:
PMC3547499
DOI:
10.1016/j.neuron.2012.11.035
[Indexed for MEDLINE]
Free PMC Article
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