Temporally induced Nurr1 can induce a non‐neuronal dopaminergic cell type in embryonic stem cell differentiation

Temporally induced Nurr1 can induce a non‐neuronal dopaminergic cell type in embryonic stem... The nuclear transcription factor Nurr1 is involved in the development and maintenance of the midbrain dopaminergic (DA) neuronal phenotype. We analysed the cellular and biological effects of Nurr1 during embryonic stem (ES) cell differentiation using the ROSA26‐engineered Tet‐inducible ES cell line J1‐rtTA that does not express transgenes in mature neurons. Induction of Nurr1 at nestin‐positive precursor and later stages of ES cell differentiation produced a non‐neuronal DA cell type including functional DA transporters. In these cells, we found a clear correlation between Nurr1 and TH gene expression and specific midbrain DA cellular markers such as AADC, AHD2 and calbindin. Nurr1 did not alter gene expression of non‐DA neuronal phenotypes and did not influence other midbrain developmental transcription factors, such as Otx1, Otx2, En‐1, GBX2, Pitx3 and lmx1b. In addition, Nurr1 expression was required for maintenance of the DA phenotype and mediated up‐regulation of the tyrosine kinase Ret and associated trophic factor GDNF‐family receptors α 1, 2, and 4. This demonstrates that Nurr1 is sufficient to induce and maintain a midbrain‐like DA biochemical and functional cellular phenotype independent of neurogenesis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Temporally induced Nurr1 can induce a non‐neuronal dopaminergic cell type in embryonic stem cell differentiation

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Publisher
Wiley
Copyright
Copyright © 2004 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1111/j.1460-9568.2004.03204.x
Publisher site
See Article on Publisher Site

Abstract

The nuclear transcription factor Nurr1 is involved in the development and maintenance of the midbrain dopaminergic (DA) neuronal phenotype. We analysed the cellular and biological effects of Nurr1 during embryonic stem (ES) cell differentiation using the ROSA26‐engineered Tet‐inducible ES cell line J1‐rtTA that does not express transgenes in mature neurons. Induction of Nurr1 at nestin‐positive precursor and later stages of ES cell differentiation produced a non‐neuronal DA cell type including functional DA transporters. In these cells, we found a clear correlation between Nurr1 and TH gene expression and specific midbrain DA cellular markers such as AADC, AHD2 and calbindin. Nurr1 did not alter gene expression of non‐DA neuronal phenotypes and did not influence other midbrain developmental transcription factors, such as Otx1, Otx2, En‐1, GBX2, Pitx3 and lmx1b. In addition, Nurr1 expression was required for maintenance of the DA phenotype and mediated up‐regulation of the tyrosine kinase Ret and associated trophic factor GDNF‐family receptors α 1, 2, and 4. This demonstrates that Nurr1 is sufficient to induce and maintain a midbrain‐like DA biochemical and functional cellular phenotype independent of neurogenesis.

Journal

European Journal of NeuroscienceWiley

Published: Mar 1, 2004

References

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