Invited Symposium: What Can Genetic Models Tell Us About Attention-Deficit Hyperactivity Disorder (ADHD)?



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Development of Midbrain Dopamine Neurons: Role of Epigenetic Factors

di Porzio, U (International Institute of Genetics and Biophysics, Naples, Italy)
Perrone-Capano, C (International Institute of Genetics and Biophysics, Naples, Italy)
Da Pozzo, P (International Institute of Genetics and Biophysics, Naples, Italy)

Contact Person: Umberto di Porzio (diporzio@iigbna.iigb.na.cnr.it)


In mammalian brains, mesencephalic dopaminergic (DA) neurons subserve complex and varied functions. Their differentiation depend on the action of two extracellular inducers, Sonic hedgehog and FGF8, which act along the ventral midbrain . After this first commitment, the function of the orphan steroid nuclear receptor Nurr1 and the homeodomain Ptx3 transcription factors is required for DA final determination. Subsequently, the maturation of DA neurotransmission follows a further complex developmental pattern of activation of genes and modulation of their product activities. DA function is selectively modulated by specific interaction with the developing target tissue. Committed and determined DA neurons express the key genes involved in DA neurotransmission at different time in development. Synthesis and accumulation of DA is achieved shortly after expression of Nurr1 and Ptx3, but dopamine transporter (DAT) gene remains repressed until DA axons reach their target. Only at this time DAT gene expression and functional uptake are detectable. Cell contacts between the presynaptic DA neurons and target striatal neurons are apparently necessary for the fine modulation of DAT expression and uptake function, in vivo and in primary cultures. Thus, cell-cell interaction has a crucial role in DA neuron maturation and maintenance.

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Presentation Number SAdi porzio0329
Keywords: substantia nigra, striatum, plasticity, primary culture, dopamine

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di Porzio, U; Perrone-Capano, C; Da Pozzo, P; (1998). Development of Midbrain Dopamine Neurons: Role of Epigenetic Factors. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/sadile/di_porzio0329/index.html
© 1998 Author(s) Hold Copyright