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First published online 5 January 2006
doi: 10.1242/dev.02224

Development 133, 507-516 (2006)
Published by The Company of Biologists 2006
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Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2

E. Andersson1,*, J. B. Jensen1,*, M. Parmar1, F. Guillemot2 and A. Björklund1,{dagger}

1 Wallenberg Neuroscience Center, Department of Experimental Medical Science, and Lund Strategic Center for Stem Cell Biology and Cell Therapy, Lund University, BMC A11, SE-221 84 Lund, Sweden.
2 National Institute for Medical Research, Division of Molecular Neurobiology, The Ridgeway, Mill Hill, London NW7 1AA, UK.

{dagger} Author for correspondence (e-mail: anders.bjorklund{at}med.lu.se)

Accepted 25 November 2005

Neurogenin 2 (Ngn2) is a proneural gene involved in neuronal differentiation and subtype specification in various regions of the nervous system. In the ventral midbrain, Ngn2 is expressed in a spatiotemporal pattern that correlates with the generation of mesencephalic dopaminergic (mesDA) neurons. We show here that lack of Ngn2 impairs the development of mesDA neurons, such that less than half of the normal mesDA neuron number remain in Ngn2 mutant mice at postnatal stages. Analysis of Ngn2 mutant mice during mesDA neurogenesis show that medially located precursors are formed but are arrested in their differentiation at a stage when they have not yet acquired the characteristics of mesDA neuron precursors. Loss of Ngn2 function appears to specifically affect the generation of DA neurons, as the development of other types of neurons within the ventral midbrain is unaltered. Ngn2 is the first example of a gene expressed in progenitors in the ventricular zone of the mesDA neuron domain that is essential for proper mesDA neuron differentiation, and whose loss of function causes impaired mesDA neurogenesis without other major abnormalities in the ventral midbrain.

Key words: Parkinson's disease, Proneural genes, Differentiation, Midbrain, Tyrosine hydroxylase, Mouse


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