The wide array of neurological disease and psychiatric disorders associated with imbalances in the catecholamine (CA) neurotransmitter systems serves to underscore their critical importance in the proper functioning of the brain. The availability of CA neurotransmitters is largely determined by regulation of the rate- limiting enzyme, tyrosine hydroxylase (TH). Studies from this laboratory have demonstrated the existence, in muscle, of an agents(s) with the unique ability to induce novel expression of the TH gene. Because of its capacity to alter the differentiative fate of certain brain neurons in culture, this factor (or combination of factors) was broadly termed muscle-derived differentiation factor (MDF). Progress over the last three years has clearly indicated the the """"""""MDF response"""""""" requires participation of at least two substances present in muscle: acidic fibroblast growth facto (aFGF) and an unidentified molecule. The investigators have found that, like the muscle agent, neurotransmitters were also important aFGF partners. Specifically, catechol-containing transmitters, which had no ability to induce TH on their own, were able to do so if co-incubated with aFGF. Studies are therefore proposed to examine the molecular processes involved in TH induction by both aFGF and the catechol neurotransmitters and the role of each in the establishment of a CA phenotype during development and in the modulation of that expression in models of disease.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Neurological Sciences Subcommittee 1 (NLS)
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Michel, Mary E
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Allegheny University of Health Sciences
Schools of Medicine
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Romano, Gaetano; Macaluso, Marcella; Lucchetti, Chiara et al. (2007) Transcription and epigenetic profile of the promoter, first exon and first intron of the human tyrosine hydroxylase gene. J Cell Physiol 211:431-8
Jin, Hao; Romano, Gaetano; Marshall, Cheryl et al. (2006) Tyrosine hydroxylase gene regulation in human neuronal progenitor cells does not depend on Nurr1 as in the murine and rat systems. J Cell Physiol 207:49-57
Romano, Gaetano; Suon, Sokreine; Jin, Hao et al. (2005) Characterization of five evolutionary conserved regions of the human tyrosine hydroxylase (TH) promoter: implications for the engineering of a human TH minimal promoter assembled in a self-inactivating lentiviral vector system. J Cell Physiol 204:666-77
Yang, Ming; Donaldson, Angela E; Marshall, Cheryl E et al. (2004) Studies on the differentiation of dopaminergic traits in human neural progenitor cells in vitro and in vivo. Cell Transplant 13:535-47
Suon, Sokreine; Jin, Hao; Donaldson, Angela E et al. (2004) Transient differentiation of adult human bone marrow cells into neuron-like cells in culture: development of morphological and biochemical traits is mediated by different molecular mechanisms. Stem Cells Dev 13:625-35
Yang, Ming; Donaldson, Angela E; Jiang, Yubao et al. (2003) Factors influencing the differentiation of dopaminergic traits in transplanted neural stem cells. Cell Mol Neurobiol 23:851-64
Kessler, Mark A; Yang, Ming; Gollomp, Kandace L et al. (2003) The human tyrosine hydroxylase gene promoter. Brain Res Mol Brain Res 112:8-23
Yang, Ming; Stull, Natalie D; Berk, Mathew A et al. (2002) Neural stem cells spontaneously express dopaminergic traits after transplantation into the intact or 6-hydroxydopamine-lesioned rat. Exp Neurol 177:50-60
Iacovitti, L; Stull, N D; Jin, H (2001) Differentiation of human dopamine neurons from an embryonic carcinomal stem cell line. Brain Res 912:99-104
Stull, N D; Iacovitti, L (2001) Sonic hedgehog and FGF8: inadequate signals for the differentiation of a dopamine phenotype in mouse and human neurons in culture. Exp Neurol 169:36-43

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