Pitx3 is Required for Development of Substantia Nigra Dopaminergic Neurons

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Mar 26

PMID 12655058

Citations 135

Authors

Irene Nunes

Lucy T Tovmasian

Robert M Silva

Robert E Burke

Stephen P Goff

Affiliations

Soon will be listed here.

Abstract

Dopaminergic (DA) neurons of substantia nigra in the midbrain control voluntary movement, and their degeneration is the cause of Parkinson's disease. The complete set of genes required to specifically determine the development of midbrain DA subgroups is not known yet. We report here that mice lacking the bicoid-related homeoprotein Pitx3 fail to develop DA neurons of the substantia nigra. Other mesencephalic DA neurons of the ventral tegmental area and retrorubral field are unaltered in their dopamine expression and histological organization. These data suggest that Pitx3-dependent gene expression is specifically required for the differentiation of DA progenitors within the mesencephalic DA system.

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References

Damier P, Hirsch E, Agid Y, Graybiel A . The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain. 1999; 122 ( Pt 8):1437-48. DOI: 10.1093/brain/122.8.1437. View

Gage P, Suh H, Camper S . The bicoid-related Pitx gene family in development. Mamm Genome. 1999; 10(2):197-200. DOI: 10.1007/s003359900970. View

Le W, Conneely O, Zou L, He Y, Saucedo-Cardenas O, Jankovic J . Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice. Exp Neurol. 1999; 159(2):451-8. DOI: 10.1006/exnr.1999.7191. View

Wallen A, Zetterstrom R, Solomin L, Arvidsson M, Olson L, Perlmann T . Fate of mesencephalic AHD2-expressing dopamine progenitor cells in NURR1 mutant mice. Exp Cell Res. 1999; 253(2):737-46. DOI: 10.1006/excr.1999.4691. View

Smidt M, Asbreuk C, Cox J, Chen H, Johnson R, Burbach J . A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci. 2000; 3(4):337-41. DOI: 10.1038/73902. View

Semina E, Murray J, Reiter R, Hrstka R, Graw J . Deletion in the promoter region and altered expression of Pitx3 homeobox gene in aphakia mice. Hum Mol Genet. 2000; 9(11):1575-85. DOI: 10.1093/hmg/9.11.1575. View

Witta J, Baffi J, Palkovits M, Mezey E, Castillo S, Nikodem V . Nigrostriatal innervation is preserved in Nurr1-null mice, although dopaminergic neuron precursors are arrested from terminal differentiation. Brain Res Mol Brain Res. 2000; 84(1-2):67-78. DOI: 10.1016/s0169-328x(00)00211-4. View

Rieger D, Reichenberger E, McLean W, Sidow A, Olsen B . A double-deletion mutation in the Pitx3 gene causes arrested lens development in aphakia mice. Genomics. 2001; 72(1):61-72. DOI: 10.1006/geno.2000.6464. View

Dunnett S, Bjorklund A, Lindvall O . Cell therapy in Parkinson's disease - stop or go?. Nat Rev Neurosci. 2001; 2(5):365-9. DOI: 10.1038/35072572. View

10.

Schultz W . Reward signaling by dopamine neurons. Neuroscientist. 2001; 7(4):293-302. DOI: 10.1177/107385840100700406. View

11.

Kawasaki H, Mizuseki K, Sasai Y . Selective neural induction from ES cells by stromal cell-derived inducing activity and its potential therapeutic application in Parkinson's disease. Methods Mol Biol. 2002; 185:217-27. DOI: 10.1385/1-59259-241-4:217. View

12.

Kawasaki H, Suemori H, Mizuseki K, Watanabe K, Urano F, Ichinose H . Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc Natl Acad Sci U S A. 2002; 99(3):1580-5. PMC: 122233. DOI: 10.1073/pnas.032662199. View

13.

Kim J, Auerbach J, Rodriguez-Gomez J, Velasco I, Gavin D, Lumelsky N . Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature. 2002; 418(6893):50-6. DOI: 10.1038/nature00900. View

14.

Varnum D, Stevens L . Aphakia, a new mutation in the mouse. J Hered. 1968; 59(2):147-50. DOI: 10.1093/oxfordjournals.jhered.a107667. View

15.

Palkovits M, Brownstein M, Saavedra J, Axelrod J . Norepinephrine and dopamine content of hypothalamic nuclei of the rat. Brain Res. 1974; 77(1):137-49. DOI: 10.1016/0006-8993(74)90810-5. View

16.

Gerfen C, Herkenham M, Thibault J . The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. J Neurosci. 1987; 7(12):3915-34. PMC: 6569093. View

17.

Seeman P, Guan H, Van Tol H . Dopamine D4 receptors elevated in schizophrenia. Nature. 1993; 365(6445):441-5. DOI: 10.1038/365441a0. View

18.

Zetterstrom R, Solomin L, Jansson L, Hoffer B, Olson L, Perlmann T . Dopamine neuron agenesis in Nurr1-deficient mice. Science. 1997; 276(5310):248-50. DOI: 10.1126/science.276.5310.248. View

19.

Smidt M, van Schaick H, Lanctot C, Tremblay J, Cox J, Van Der Kleij A . A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergic neurons. Proc Natl Acad Sci U S A. 1997; 94(24):13305-10. PMC: 24304. DOI: 10.1073/pnas.94.24.13305. View

20.

Saucedo-Cardenas O, Quintana-Hau J, Le W, Smidt M, Cox J, De Mayo F . Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci U S A. 1998; 95(7):4013-8. PMC: 19954. DOI: 10.1073/pnas.95.7.4013. View