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First published online February 18, 2004
doi: 10.1242/10.1242/dev.01022
1 Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and
Anatomy, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The
Netherlands
2 GSF, Institute of Developmental Genetics, Ingolstaedter Landstrasse 1, D-85764
München, Germany
* Author for correspondence (e-mail: m.p.smidt{at}med.uu.nl)
Accepted 28 November 2003
The mesencephalic dopamine (mesDA) system is involved in the control of movement and behavior. The expression of Pitx3 in the brain is restricted to the mesDA system and the gene is induced relatively late, at E11.5, a time when tyrosine hydroxylase (Th) gene expression is initiated. We show here that, in the Pitx3-deficient aphakia (ak) mouse mutant, the mesDA system is malformed. Owing to the developmental failure of mesDA neurons in the lateral field of the midbrain, mesDA neurons are not found in the SNc and the projections to the caudate putamen are selectively lost. However, Pitx3 is expressed in all mesDA neurons in control animals. Therefore, mesDA neurons react specifically to the loss of Pitx3. Defects of motor control where not seen in the ak mice, suggesting that other neuronal systems compensate for the absence of the nigrostriatal pathway. However, an overall lower activity was observed. The results suggest that Pitx3 is specifically required for the formation of the SNc subfield at the onset of dopaminergic neuron differentiation.
Key words: Mesencephalic, Dopaminergic, Pitx3, Substantia nigra
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