Dopaminergic properties and function after grafting of attached neural precursor cultures

Timmer, Marco; Großkreutz, Julian; Schlesinger, Friedrich; Kenn, Klaus; Wesemann, Maike; Just, Lothar; Bufler, J.; Grothe, Claudia

doi:10.1016/j.nbd.2005.09.003

Cited by 40 publications

(50 citation statements)

References 61 publications

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“…Nuclear Accumulation of FGFR1 in Differentiating Primary Ventral Midbrain Progenitor Cells-Consistent with these in vivo observations, in vitro experiments using a standard differentiation protocol for primary rat E12.5 ventral mesencephalic progenitor cells (29) showed a differential subcellular distribution of FGFR1 during the process of differentiation (Fig. 2B).…”

Section: Fgfr1 and Nurr1 Localize To Nuclei Of Developing Dasupporting

confidence: 76%

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Cooperation of Nuclear Fibroblast Growth Factor Receptor 1 and Nurr1 Offers New Interactive Mechanism in Postmitotic Development of Mesencephalic Dopaminergic Neurons

Baron

Förthmann

Lee

et al. 2012

Journal of Biological Chemistry

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Background: Nurr1 and FGFR1 are integrative nuclear factors participating in postmitotic dopaminergic neuron development. Results: Both nuclear receptors show a functional interaction in co-immunoprecipitation, FRAP, ChIP, and luciferase gene reporter assay. Conclusion: Cooperation of nuclear FGFR1 and Nurr1 offers a new mechanism in transcriptional regulation and integration. Significance: This mechanism may channel diverse stimuli in developing and mature dopaminergic neurons, providing a potential therapeutic target.

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Section: Fgfr1 and Nurr1 Localize To Nuclei Of Developing Dasupporting

confidence: 76%

“…The primary cells of ventral mesencephalon were dissected from E12.5 rat embryos and cultured as described previously (29). The cells were cultured for 2 days in proliferation medium and for either 1 or 4 days in vitro (DIV) in differentiation medium.…”

Section: Methodsmentioning

confidence: 99%

Cooperation of Nuclear Fibroblast Growth Factor Receptor 1 and Nurr1 Offers New Interactive Mechanism in Postmitotic Development of Mesencephalic Dopaminergic Neurons

Baron

Förthmann

Lee

et al. 2012

Journal of Biological Chemistry

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“…Additional evidence for the feasibility of viable dissociation and purification of mature, postmitotic neurons by FACS was provided in recent studies where corticospinal motor neurons from P3-P6 pups [46,47] and striatal projection neurons from 2-month-old pups [48] were isolated. It is also evident that primary dopamine neurons can survive dissociation after in vitro culture prior to transplantation, within a certain time window [49]. This shows that even neurons that have extended long processes in vivo and/or in vitro can survive dissociation.…”

Section: Discussionmentioning

confidence: 97%

Selection of Embryonic Stem Cell-Derived Enhanced Green Fluorescent Protein-Positive Dopamine Neurons Using the Tyrosine Hydroxylase Promoter Is Confounded by Reporter Gene Expression in Immature Cell Populations

et al. 2007

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Transplantation of mouse embryonic stem (mES) cells can restore function in Parkinson disease models, but can generate teratomas. Purification of dopamine neurons derived from embryonic stem cells by fluorescence-activated cell sorting (FACS) could provide a functional cell population for transplantation while eliminating the risk of teratoma formation. Here we used the tyrosine hydroxylase (TH) promoter to drive enhanced green fluorescent protein (eGFP) expression in mES cells. First, we evaluated 2.5-kilobase (kb) and 9-kb TH promoter fragments and showed that clones generated using the 9-kb fragment produced significantly more eGFP؉/TH؉ neurons. We selected the 9-kb TH clone with the highest eGFP/TH overlap for further differentiation, FACS, and transplantation experiments. Grafts contained large numbers of eGFP؉ dopamine neurons of an appropriate phenotype. However, there were also numerous eGFP؉ cells that did not express TH and did not have a neuronal morphology. In addition, we found cells in the grafts representing all three germ layers. Based on these findings, we examined the expression of stem cell markers in our eGFP؉ population. We found that a majority of eGFP؉ cells were stagespecific embryonic antigen-positive (SSEA-1؉) and that the genetically engineered clones contained more SSEA-1؉ cells after differentiation than the original D3 mES cells. By negative selection of SSEA-1, we could isolate a neuronal eGFP؉ population of high purity. These results illustrate the complexity of using genetic selection to purify mES cell-derived dopamine neurons and provide a comprehensive analysis of cell selection strategies based on tyrosine hydroxylase expression.

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“…FGF-2 level is reciprocal to number of DA neurons FGF-2 is a potent survival factor and is, for example, used as mitogen for the expansion of DA progenitor cells in vitro (Studer et al, 1998;Timmer et al, 2006) and promotes the survival of grafted embryonic DA neurons in vivo (Mayer et al, 1993b;Timmer et al 2004). However, only little is known about the physiological role of FGF-2 on DA neurons and the nigrostriatal system.…”

Section: Dg)mentioning

confidence: 99%

Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion

Cesnulevicius²,

et al. 2007

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Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (ϩ/Ϫ) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase expression and a reduced DA cell density. The volumes of the substantia nigra were enlarged in both FGF-2 Ϫ/Ϫ and in FGF-2 transgenic mice, suggesting an important role of FGF-2 for the establishment of the proper number of DA neurons and a normal sized substantia nigra during development. In a second set of experiments, the putative relevance of endogenous FGF-2 after neurotoxin application was investigated regarding the number of rescued DA neurons after partial 6-OHDA lesion. Interestingly, the results after lesion were directly opposed to the results after development: significantly less DA neurons survived in FGF-2 Ϫ/Ϫ mice compared with wild-type mice. Together, the results indicate that FGFR3 is crucially involved in regulating the number of DA neurons. The lack of FGF-2 seems to be (over)compensated during development, but, after lesion, compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2 protects DA neurons from 6-OHDA neurotoxicity.

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Dopaminergic properties and function after grafting of attached neural precursor cultures

Cited by 40 publications

References 61 publications

Cooperation of Nuclear Fibroblast Growth Factor Receptor 1 and Nurr1 Offers New Interactive Mechanism in Postmitotic Development of Mesencephalic Dopaminergic Neurons

Cooperation of Nuclear Fibroblast Growth Factor Receptor 1 and Nurr1 Offers New Interactive Mechanism in Postmitotic Development of Mesencephalic Dopaminergic Neurons

Selection of Embryonic Stem Cell-Derived Enhanced Green Fluorescent Protein-Positive Dopamine Neurons Using the Tyrosine Hydroxylase Promoter Is Confounded by Reporter Gene Expression in Immature Cell Populations

Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion

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