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Differentiation of Mouse Embryonic Stem Cells into Cortical Interneuron Precursors
Published on: December 3, 2017
NKX2.1 specifies cortical interneuron fate by activating Lhx6
Tonggong Du1, Qing Xu, Polloneal J Ocbina
1Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, USA.
Development (Cambridge, England)
|March 15, 2008
Summary
Transcription factor NKX2.1 is crucial for specifying cortical interneurons. It directly activates the Lhx6 gene, which is essential for rescuing parvalbumin and somatostatin interneuron deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- The medial ganglionic eminence (MGE) in the ventral telencephalon is a primary source of cortical interneurons.
- The transcription factor NKX2.1 is essential for specifying parvalbumin (PV) and somatostatin (SST) interneuron subtypes, but its direct targets are unknown.
Purpose of the Study:
- To identify direct targets of NKX2.1 in cortical interneuron development.
- To elucidate the molecular mechanisms by which NKX2.1 regulates interneuron specification.
Main Methods:
- Slice culture electroporation of Nkx2.1 cDNA in Nkx2.1-/- mouse embryos.
- Transplantation of modified cells into neonatal mouse cortex for postnatal fate analysis.
- Gain- and loss-of-function studies of the Lhx6 gene.
- Chromatin immunoprecipitation to assess NKX2.1 binding to the Lhx6 promoter.
Main Results:
- NKX2.1 expression in MGE is required for PV and SST interneuron development.
- Lhx6 is induced upon Nkx2.1 rescue and is necessary and sufficient for rescuing interneuron phenotypes.
- NKX2.1 directly binds to a conserved sequence in the Lhx6 promoter, activating its expression.
Conclusions:
- Lhx6 is a direct downstream target of NKX2.1 in cortical interneuron specification.
- NKX2.1 regulates interneuron fate through the transcriptional activation of Lhx6.
- Novel slice transfection and transplantation methods facilitate the study of early neuronal fate mechanisms.
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