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Molecular players in the development and maintenance of mesencephalic dopamine systems

Published online by Cambridge University Press:  18 September 2015

Extract

Several psychiatric diseases are considered to be neuro-developmental disorders. Amongst these are schizophrenia and autism, in which genetic and environmental components have been indicated. In these disorders intrinsic molecular mechanisms of brain development may be deranged due to genetic predispositions, or modified by external influences. Brain development is a delicate process of well-tuned cellular proliferation and differentiation of multipotent neural progenitor cells driven by spatiotemporal cues. One of the fundamental mechanisms is the interaction between external signals, e.g. growth factors, and internal regulators, e.g. transcription factors. An important transmitter system involved in behavioural and affective functions relevant for psychiatric disorders is the mesencephalic dopamine (DA) system. The mesencephalic DA system is organized in two anatomically and functionally different systems. DA neurons in the ventral tegmental area project to the mesolimbic system and are mostly related to control of behaviour. It has been implicated in drug addiction and affective disorders like dipolar disorder and schizophrenia. The dopamine system of the substantia nigra (nigro-striatal pathway) is implicated in movement control. Degeneration of this system, as in Parkinson's disease, or altered function in tardive dyskinesia have highlighted its importance in human disease. Recent findings in molecular neurobiology have provided the first clues to molecular mechanisms involved in developing and mature DA neurons. These may have clinical implications in novel therapeutic strategies.

Type
Research Article
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 1999

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References

Literature

1.Ye, W, Shimamura, K, Rubenstein, JL, et al.FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 1998;93;755–66.CrossRefGoogle ScholarPubMed
2.Zetterstrom, RH, Solomin, L, Jansson, L, et al.Dopamine neuron agenesis in Nurrl-deficient mice. Science 1997;276;248–50.CrossRefGoogle ScholarPubMed
3.Saucedo-Cardenas, O, Quintana-Hau, JD, Le, WD, et al.Nurrl is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc natl Acad Sci USA 1998;95;4013–8.CrossRefGoogle Scholar
4.Zetterstrom, RH, Solomin, L, Mitsiadis, T, et al.Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurrl, and Nor 1. Mol Endocrinol 1996; 10:1656–66.Google Scholar
5.Smidt, MP, Schaick, HS van, Lanctot, C, et al.A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergic neurons. Proc natl Acad Sci USA 1997;94;13305–10.CrossRefGoogle ScholarPubMed
6.Drouin, J, Lamolet, B, Lamonerie, T, et al.The PTX family of homeodomain transcription factors during pituitary developments. Mol cell Endocrinol 1998;140;31–6.CrossRefGoogle ScholarPubMed
7.Semina, EV, Reiter, R, Leysens, NJ, et al.Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet 1996;14;392–9.CrossRefGoogle ScholarPubMed
8.Yoshioka, H, Meno, C, Koshiba, K, et al.Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry. Cell 1998;94;299305.CrossRefGoogle Scholar
9.Semina, EV, Reiter, RS, Murray, JC. Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19. Hum mol Genet 1997;6;2109–16.CrossRefGoogle Scholar
10.Semina, EV, Ferrell, RE, Mintz-Hittner, HA, et al.A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Nat Genet 1998;19;167–70.CrossRefGoogle ScholarPubMed