QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 6, 2005, 25(27):6467-6477; doi:10.1523/JNEUROSCI.1676-05.2005

This Article Full Text Full Text (PDF) A correction has been published Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (46) Citing Articles via Google Scholar Google Scholar Articles by Thompson, L. Articles by Björklund, A. Search for Related Content PubMed PubMed Citation Articles by Thompson, L. Articles by Björklund, A.

 Previous Article

Development/Plasticity/Repair
Identification of Dopaminergic Neurons of Nigral and Ventral Tegmental Area Subtypes in Grafts of Fetal Ventral Mesencephalon Based on Cell Morphology, Protein Expression, and Efferent Projections

Lachlan Thompson, Perrine Barraud, Elin Andersson, Deniz Kirik, and Anders Björklund

Wallenberg Neuroscience Center, Department of Experimental Medical Research, and Lund Strategic Center for Stem Cell Biology and Cell Therapy, Lund University, SE-221 84 Lund, Sweden

Transplants of fetal ventral mesencephalic tissue are known to contain a mixture of two major dopamine (DA) neuron types: the A9 neurons of the substantia nigra pars compacta (SNpc) and the A10 neurons of the ventral tegmental area (VTA). Previous studies have suggested that these two DA neuron types may differ in their growth characteristics, but, because of technical limitations, it has so far been difficult to identify the two subtypes in fetal ventral mesencephalon (VM) grafts and trace their axonal projections. Here, we have made use of a transgenic mouse expressing green fluorescent protein (GFP) under the tyrosine hydroxylase promoter. The expression of the GFP reporter allowed for visualization of the grafted DA neurons and their axonal projections within the host brain. We show that the SNpc and VTA neuron subtypes in VM grafts can be identified on the basis of their morphology and location within the graft, and their expression of a G-protein-gated inwardly rectifying K⁺ channel subunit (Girk2) and calbindin, respectively, and also that the axonal projections of the two DA neuron types are markedly different. By retrograde axonal tracing, we show that dopaminergic innervation of the striatum is derived almost exclusively from the Girk2-positive SNpc cells, whereas the calbindin-positive VTA neurons project to the frontal cortex and probably also other forebrain areas. The results suggest the presence of axon guidance and target recognition mechanisms in the DA-denervated forebrain that can guide the growing axons to their appropriate targets and indicate that cell preparations used for cell replacement in Parkinson's disease will be therapeutically useful only if they contain cells capable of generating the correct nigral DA neuron phenotype.

Key words: tyrosine hydroxylase; green fluorescent protein; GFP; calbindin; Girk2; Parkinson's disease; transplantation

---

Received April 27, 2005; revised May 30, 2005; accepted June 2, 2005.

This article has been cited by other articles:

				S. M. Kolk, R.-A. F. Gunput, T. S. Tran, D. M. A. van den Heuvel, A. A. Prasad, A. J. C. G. M. Hellemons, Y. Adolfs, D. D. Ginty, A. L. Kolodkin, J. P. H. Burbach, et al. Semaphorin 3F Is a Bifunctional Guidance Cue for Dopaminergic Axons and Controls Their Fasciculation, Channeling, Rostral Growth, and Intracortical Targeting J. Neurosci., October 7, 2009; 29(40): 12542 - 12557. [Abstract] [Full Text] [PDF]

				S. Friling, E. Andersson, L. H. Thompson, M. E. Jonsson, J. B. Hebsgaard, E. Nanou, Z. Alekseenko, U. Marklund, S. Kjellander, N. Volakakis, et al. Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells PNAS, May 5, 2009; 106(18): 7613 - 7618. [Abstract] [Full Text] [PDF]

				A. Vinuela, P. J. Hallett, C. Reske-Nielsen, M. Patterson, T. D. Sotnikova, M. G. Caron, R. R. Gainetdinov, and O. Isacson Implanted reuptake-deficient or wild-type dopaminergic neurons improve ON L-dopa dyskinesias without OFF-dyskinesias in a rat model of Parkinson's disease Brain, December 1, 2008; 131(12): 3361 - 3379. [Abstract] [Full Text] [PDF]

				F. E. O'Keeffe, S. A. Scott, P. Tyers, G. W. O'Keeffe, J. W. Dalley, R. Zufferey, and M. A. Caldwell Induction of A9 dopaminergic neurons from neural stem cells improves motor function in an animal model of Parkinson's disease Brain, March 1, 2008; 131(3): 630 - 641. [Abstract] [Full Text] [PDF]

				S.-L. Ang Transcriptional control of midbrain dopaminergic neuron development Development, September 15, 2006; 133(18): 3499 - 3506. [Abstract] [Full Text] [PDF]

				P. Soundararajan, G. B. Miles, L. L. Rubin, R. M. Brownstone, and V. F. Rafuse Motoneurons derived from embryonic stem cells express transcription factors and develop phenotypes characteristic of medial motor column neurons. J. Neurosci., March 22, 2006; 26(12): 3256 - 3268. [Abstract] [Full Text] [PDF]

				S. Johansson, I-H. Lee, L. Olson, and C. Spenger Olfactory ensheathing glial co-grafts improve functional recovery in rats with 6-OHDA lesions Brain, December 1, 2005; 128(12): 2961 - 2976. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help