NKX2.1 specifies cortical interneuron fate by activating Lhx6
Author:
Du Tonggong1, Xu Qing1, Ocbina Polloneal J.1, Anderson Stewart A.1
Affiliation:
1. 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.
Abstract
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.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference50 articles.
1. Alcantara, S., de Lecea, L., Del Rio, J. A., Ferrer, I. and Soriano, E. (1996). Transient colocalization of parvalbumin and calbindin D28k in the postnatal cerebral cortex: evidence for a phenotypic shift in developing nonpyramidal neurons. Eur. J. Neurosci.8,1329-1339. 2. Alifragis, P., Liapi, A. and Parnavelas, J. G.(2004). Lhx6 regulates the migration of cortical interneurons from the ventral telencephalon but does not specify their GABA phenotype. J. Neurosci.24,5643-5648. 3. Alvarez-Dolado, M., Calcagnotto, M. E., Karkar, K. M.,Southwell, D. G., Jones-Davis, D. M., Estrada, R. C., Rubenstein, J. L.,Alvarez-Buylla, A. and Baraban, S. C. (2006). Cortical inhibition modified by embryonic neural precursors grafted into the postnatal brain. J. Neurosci.26,7380-7389. 4. Butt, S. J., Fuccillo, M., Nery, S., Noctor, S., Kriegstein, A.,Corbin, J. G. and Fishell, G. (2005). The temporal and spatial origins of cortical interneurons predict their physiological subtype. Neuron48,591-604. 5. Cobos, I., Calcagnotto, M. E., Vilaythong, A. J., Thwin, M. T.,Noebels, J. L., Baraban, S. C. and Rubenstein, J. L. (2005). Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nat. Neurosci.8,1059-1068.
Cited by
206 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|