Present address: Wolfson Institute for Biomedical Research, University College of London, London, UK.
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The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1
Article first published online: 18 NOV 2011
DOI: 10.1111/j.1460-9568.2011.07890.x
© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
Additional Information
How to Cite
Magno, L., Kretz, O., Bert, B., Ersözlü, S., Vogt, J., Fink, H., Kimura, S., Vogt, A., Monyer, H., Nitsch, R. and Naumann, T. (2011), The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1. European Journal of Neuroscience, 34: 1767–1782. doi: 10.1111/j.1460-9568.2011.07890.x
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Present address: Wolfson Institute for Biomedical Research, University College of London, London, UK.
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R.N. and T.N. contributed equally to this work.
Publication History
- Issue published online: 28 NOV 2011
- Article first published online: 18 NOV 2011
- Received 4 June 2011, revised 16 August 2011, accepted 2 September 2011
- Abstract
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- References
- Cited By
Keywords:
- choline acetyltransferase;
- choreoathetosis;
- human;
- mouse;
- parvalbumin
Abstract
The transcription factor Nkx2-1 belongs to the homeobox-encoding family of proteins that have essential functions in prenatal brain development. Nkx2-1 is required for the specification of cortical interneurons and several neuronal subtypes of the ventral forebrain. Moreover, this transcription factor is involved in migratory processes by regulating the expression of guidance molecules. Interestingly, Nkx2-1 expression was recently detected in the mouse brain at postnatal stages. Using two transgenic mouse lines that allow prenatal or postnatal cell type-specific deletion of Nkx2-1, we show that continuous expression of the transcription factor is essential for the maturation and maintenance of cholinergic basal forebrain neurons in mice. Notably, prenatal deletion of Nkx2-1 in GAD67-expressing neurons leads to a nearly complete loss of cholinergic neurons and parvalbumin-containing GABAergic neurons in the basal forebrain. We also show that postnatal mutation of Nkx2-1 in choline acetyltransferase-expressing cells causes a striking reduction in their number. These degenerative changes are accompanied by partial denervation of their target structures and results in a discrete impairment of spatial memory.