HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) The FASEB Journal_Park et al_Supplemental Figures and Tables All Versions of this Article: fj.06-6159fjev1 20/14/2553    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, C.-H. Articles by Lee, S.-H. Search for Related Content PubMed PubMed Citation Articles by Park, C.-H. Articles by Lee, S.-H.

Acquisition of in vitro and in vivo functionality of Nurr1-induced dopamine neurons

Chang-Hwan Park^*,, Jin Sun Kang^*,, Yeon Ho Shin^*,, Mi-Yoon Chang^,, Seungsoo Chung^||, Hyun-Chul Koh^,, Mei Hong Zhu^¶, Seog Bae Oh^¶, Yong-Sung Lee^,, Georgia Panagiotakos^**, Vivian Tabar^**, Lorenz Studer^** and Sang-Hun Lee^,,1

Departments of
^* Microbiology,

Biochemistry and Molecular Biology, and

Pharmacology, College of Medicine, and

Institute of Mental Health, Hanyang University, Seoul, Korea;

^|| Department of Physiology, College of Medicine, Yonsei University, Seoul, Korea;

^¶ Department of Physiology, College of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea; and

^** Laboratory of Stem Cell and Tumor Biology, Neurosurgery and Developmental Biology, Sloan Kettering Cancer Institute, New York, New York, USA

¹Correspondence: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, #17 Haengdang-dong, Sungdong-gu, Seoul 133–791, Korea. E-mail: leesh{at}hanyang.ac.kr

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.—Park, C.-H., Kang, J. S., Shin, Y. H., Chang, M.-Y., Chung, S., Koh, H.-C., Zhu, M. H., Oh, S. B., Lee, Y.-S., Panagiotakos, G., Tabar, V., Studer, L., and Lee, S.-H. Acquisition of in vitro and in vivo functionality of Nurr1-induced dopamine neurons.

This article has been cited by other articles:

				J.-W. Shim, C.-H. Park, Y.-C. Bae, J.-Y. Bae, S. Chung, M.-Y. Chang, H.-C. Koh, H.-S. Lee, S.-J. Hwang, K.-H. Lee, et al. Generation of Functional Dopamine Neurons from Neural Precursor Cells Isolated from the Subventricular Zone and White Matter of the Adult Rat Brain Using Nurr1 Overexpression Stem Cells, May 1, 2007; 25(5): 1252 - 1262. [Abstract] [Full Text] [PDF]