Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3

M. Smidt, S. Smits, H. Bouwmeester, F. Hamers, A. Hellemons, J.P.H. Burbach

    Research output: Contribution to journalArticleAcademicpeer-review

    249 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)1145-1155
    JournalDevelopment
    Volume131
    Issue number5
    DOIs
    Publication statusPublished - 2004

    Keywords

    • nail-patella syndrome
    • lmx1b mutant mice
    • transcription factor
    • aphakia mice
    • limb development
    • lens development
    • homeobox gene
    • binding-site
    • neural-tube
    • midbrain

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