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doi: 10.1242/10.1242/dev.00464

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Development 130, 2535-2542 (2003)
Copyright © 2003 The Company of Biologists Limited

DEVELOPMENT AND DISEASE

Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons

Pepijn van den Munckhof1,*, Kelvin C. Luk2,*, Line Ste-Marie3, Jane Montgomery3, Pierre J. Blanchet4, Abbas F. Sadikot2,{dagger} and Jacques Drouin1,{dagger}

1 Unité de recherche en génétique moléculaire, Institut de recherches cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada
2 Cone Laboratory, Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada
3 Laboratoire de neurobiologie, Centre de recherche, CHUM Hôpital Notre-Dame, Université de Montréal, Montréal QC H2L 4M1, Canada
4 Centre de recherche, CHUM Hôpital Saint-Luc, Université de Montréal, Montréal QC H2X 3J4, Canada

{dagger} Authors for correspondence (e-mail: drouinj{at}ircm.qc.ca and sadikot{at}bic.mni.mcgill.ca)

Accepted 4 March 2003

Mesencephalic dopaminergic (MesDA) neurons play crucial roles in motor and behavioral processes; their loss in Parkinson's disease (PD) results in striatal dopamine (DA) deficiency and hypokinetic movement disorder. The Pitx3 homeobox gene is expressed in the MesDA system. We now show that only a subset of MesDA neurons express Pitx3 and that in Pitx3-deficient aphakia mice, this subset is progressively lost by apoptosis during fetal (substantia nigra, SN) and postnatal (ventral tegmental area) development, resulting in very low striatal DA and akinesia. Similar to human PD, dorsal SN neurons (which are Pitx3 negative) are spared in mutant mice. Thus, Pitx3 defines a pathway for survival of neurons that are implicated in PD and that are required for spontaneous locomotor activity.

Key words: Homeobox, Transcription factor, Pitx3 (Ptx3), Midbrain, Dopamine




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