Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons-Reference-Cited by-同舟云学术

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

Published:2003-06-01 Issue:11 Volume:130 Page:2535-2542
ISSN:1477-9129
Container-title:Development
language:en
Short-container-title:

Author:

van den Munckhof Pepijn¹,Luk Kelvin C.²,Ste-Marie Line³,Montgomery Jane³,Blanchet Pierre J.⁴,Sadikot Abbas F.²,Drouin Jacques¹

Affiliation:

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

Abstract

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.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

Link

http://journals.biologists.com/dev/article-pdf/130/11/2535/1143202/2535.pdf

Reference38 articles.

1. Amendt, B. A., Sutherland, L. B., Semina, E. V. and Russo, A. F. (1998). The molecular basis of Rieger syndrome. analysis of Pitx2 homeodomain protein activities. J. Biol. Chem.273,20066-20072.

2. Bayer, S. A., Wills, K. V., Triarhou, L. C., Verina, T., Thomas,J. D. and Ghetti, B. (1995). Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice. Proc. Natl. Acad. Sci. USA92,9137-9140.

3. Björklund, A. and Lindvall, O., eds(1984). Dopamine containing systems in the CNS. In Handbook of Chemical Neuroanatomy, pp.55-122. Amsterdam: Elsevier.

4. Chen, H., Lun, Y., Ovchinnikov, D., Kokubo, H., Oberg, K. C.,Pepicelli, C. V., Gan, L., Lee, B. and Johnson, R. L.(1998). Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat. Genet.19,51-55.

5. Dawson, T., Mandir, A. and Lee, M. (2002). Animal models of PD: pieces of the same puzzle? Neuron35,219-222.

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