Acquisition of in vitro and in vivo functionality of Nurr1-induced dopamine neurons Journal Article
| Authors: | Park, C. H.; Jin, S. K.; Yeon, H. S.; Chang, M. Y.; Chung, S.; Koh, H. C.; Mei, H. Z.; Seog, B. O.; Lee, Y. S.; Panagiotakos, G.; Tabar, V.; Studer, L.; Lee, S. H. |
| Article Title: | Acquisition of in vitro and in vivo functionality of Nurr1-induced dopamine neurons |
| Abstract: | Neural precursor cells provide an expandable source of neurons and glia for basic and translational applications. However, little progress has been made in directing naive neural precursors toward specific neuronal fates such as midbrain dopamine (DA) neurons. We have recently demonstrated that transgenic expression of the nuclear orphan receptor Nurr1 is sufficient to drive dopaminergic differentiation of forebrain embryonic rat neural precursors in vitro. However, Nurr1-induced DA neurons exhibit immature neuronal morphologies and functional properties and are unable to induce behavioral recovery in rodent models of Parkinson's disease (PD). Here, we report on the identification of key genetic factors that drive morphological and functional differentiation of Nurr1-derived DA neurons. We show that coexpression of Nurr1, Bcl-XL, and Sonic hedgehog (SHH) or Nurr1 and the proneural bHLH factor Mash1 is sufficient to drive naive rat forebrain precursors into neurons exhibiting the biochemical, electrophysiological, and functional properties of DA neuron in vitro. On transplantation into the striatum of Parkinsonian rats, precursor cells engineered with Nurr1/SHH/Bcl-XL or Nurr1/Mash1 survived in vivo and differentiated into mature DA neurons that can reverse the behavioral deficits in the grafted animals. © FASEB. |
| Keywords: | controlled study; nonhuman; animal cell; animal tissue; cell function; heredity; sonic hedgehog protein; animal experiment; animal model; in vivo study; in vitro study; protein bcl xl; transplantation; animalia; rat; rodentia; parkinson disease; nerve cell differentiation; sonic hedgehog; erinaceidae; dopaminergic nerve cell; nuclear receptor related factor 1; bcl-xl; parkinson's disease; parkinsonia; transcription factor mash1; dopamine neuron; dopaminergic differentiation; mash1; neural precursor cell |
| Journal Title: | FASEB Journal |
| Volume: | 20 |
| Issue: | 14 |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2006-12-01 |
| Start Page: | E1910 |
| End Page: | E1923 |
| Language: | English |
| DOI: | 10.1096/fj.06-6159fje |
| PROVIDER: | scopus |
| PUBMED: | 17077287 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 17" - "Export Date: 4 June 2012" - "CODEN: FAJOE" - "Source: Scopus" |
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13Panagiotakos
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