Fate of Mesencephalic AHD2-Expressing Dopamine Progenitor Cells in Nurr1 Mutant Mice

Fate of Mesencephalic AHD2-Expressing Dopamine Progenitor Cells in Nurr1 Mutant Mice The orphan nuclear receptor NURR1 was previously demonstrated to be required for the generation of mesencephalic dopamine (DA) cells. However, even in the absence of NURR1, which is normally expressed as cells become postmitotic, neuronal differentiation is induced and expression of several genes detected in developing dopamine cells appears normal during early stages of development. These include the homeobox transcription factors engrailed and Ptx-3 as well as aldehyde dehydrogenase 2, here defined as the earliest marker identified in developing DA cells, expressed already in mitotic DA progenitors. We have used the expression of these dopaminergic markers, retrograde axonal tracing, and apoptosis analyses to study the fate of the DA progenitor cells in the absence of NURR1. We conclude that NURR1 plays a critical role in the maturation, migration, striatal target area innervation, and survival of differentiating mesencephalic DA cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Cell Research Elsevier

Fate of Mesencephalic AHD2-Expressing Dopamine Progenitor Cells in Nurr1 Mutant Mice

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Publisher
Elsevier
Copyright
Copyright © 1999 Academic Press
ISSN
0014-4827
DOI
10.1006/excr.1999.4691
Publisher site
See Article on Publisher Site

Abstract

The orphan nuclear receptor NURR1 was previously demonstrated to be required for the generation of mesencephalic dopamine (DA) cells. However, even in the absence of NURR1, which is normally expressed as cells become postmitotic, neuronal differentiation is induced and expression of several genes detected in developing dopamine cells appears normal during early stages of development. These include the homeobox transcription factors engrailed and Ptx-3 as well as aldehyde dehydrogenase 2, here defined as the earliest marker identified in developing DA cells, expressed already in mitotic DA progenitors. We have used the expression of these dopaminergic markers, retrograde axonal tracing, and apoptosis analyses to study the fate of the DA progenitor cells in the absence of NURR1. We conclude that NURR1 plays a critical role in the maturation, migration, striatal target area innervation, and survival of differentiating mesencephalic DA cells.

Journal

Experimental Cell ResearchElsevier

Published: Dec 15, 1999

References

  • Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene
    Castillo, S.O.; Baffi, J.S.; Palkovits, M.; Goldstein, D.S.; Kopin, I.J.; Witta, J.; Magnuson, M.A.; Nikodem, V.M.
  • Specification of dopaminergic and serotonergic neurons in the vertebrate CNS
    Hynes, M.; Rosenthal, A.
  • Molecular identification of the 62 kd form of glutamic acid decarboxylase from the mouse
    Katarova, Z.; Szabo, G.; Mugnaini, E.; Greenspan, R.
  • Organization, sequence, chromosomal localization, and promoter identification of the mouse orphan nuclear receptor nurr1 gene
    Castillo, S.O.; Xiao, Q.X.; Lyu, M.S.; Kozak, C.A.; Nikodem, V.M.
  • Role of retinoids in the CNS: Differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid
    Zetterström, R.H.; Lindqvist, E.; Mata de Urquiza, A.; Tomac, A.; Eriksson, U.; Perlmann, T.; Olson, L.

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