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The Journal of Neuroscience, April 22, 2009, 29(16):5170-5182; doi:10.1523/JNEUROSCI.5569-08.2009

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Development/Plasticity/Repair
Ventral Mesencephalon-Enriched Genes That Regulate the Development of Dopaminergic Neurons In Vivo

Min Yin,^1,2 * Shuxi Liu,^2 * Yanqing Yin,² Sen Li,² Zhihua Li,¹ Xuefei Wu,¹ Bo Zhang,² Siew-Lan Ang,³ Yuqiang Ding,² and Jiawei Zhou²

¹Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, and ²State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and ³Division of Developmental Neurobiology, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom

Correspondence should be addressed to Dr. Jiawei Zhou, Institute of Neuroscience, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Email: jwzhou{at}ion.ac.cn

Mesodiencephalic dopaminergic (mDA) neurons are critical for movement control and other physiological activities. However, the molecular mechanisms underlying their development are poorly understood. We aimed to establish the expression profiles of genes involved in this process and unravel genetic programs that control late development of mDA neurons. We compared genome-wide gene expression profiles of developing mouse ventral mesencephalon (VM) using microarrays. We identified a set of genes that show spatially and temporally restricted expression in the VM in an Ngn2 (neurogenin 2)-dependent manner and are potentially important for mDA neuron development. Functional analysis on mice lacking the VM-specific gene early B-cell factor 1 (Ebf1) revealed that Ebf1 is essential for the terminal migration of mDA neurons in the substantia nigra pars compacta. Thus, we identified a set of VM-enriched genes that are important for mDA neuron development. Our analysis also provides a genetic framework for further investigation of the molecular mechanisms mediating mDA neuron development.

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Received Nov. 20, 2008; accepted Feb. 7, 2009.

Correspondence should be addressed to Dr. Jiawei Zhou, Institute of Neuroscience, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Email: jwzhou{at}ion.ac.cn

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