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First published online 15 December 2008
doi: 10.1242/dev.029900

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.029900v1 dev.029900v2 136/2/253    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development 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 Kala, K. Articles by Partanen, J. Search for Related Content PubMed PubMed Citation Articles by Kala, K. Articles by Partanen, J. Social Bookmarking                         What's this?

Gata2 is a tissue-specific post-mitotic selector gene for midbrain GABAergic neurons

¹ Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
² Division of Biochemistry, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
³ Department of Developmental Biology and Department of Physiology, University of Tartu, 50090 Tartu, Estonia.
⁴ Helmholtz Zentrum München, Institute of Developmental Genetics, D-85764 Neuherberg, Germany.

^* Author for correspondence (e-mail: Juha.M.Partanen{at}Helsinki.Fi)

Accepted 10 November 2008

Midbrain GABAergic neurons control several aspects of behavior, but regulation of their development and diversity is poorly understood. Here, we further refine the midbrain regions active in GABAergic neurogenesis and show their correlation with the expression of the transcription factor Gata2. Using tissue-specific inactivation and ectopic expression, we show that Gata2 regulates GABAergic neuron development in the mouse midbrain, but not in rhombomere 1, where it is needed in the serotonergic lineage. Without Gata2, all the precursors in the embryonic midbrain fail to activate GABAergic neuron-specific gene expression and instead switch to a glutamatergic phenotype. Surprisingly, this fate switch is also observed throughout the neonatal midbrain, except for the GABAergic neurons located in the ventral dopaminergic nuclei, suggesting a distinct developmental pathway for these neurons. These studies identify Gata2 as an essential post-mitotic selector gene of the GABAergic neurotransmitter identity and demonstrate developmental heterogeneity of GABAergic neurons in the midbrain.

Key words: GABA, Interneuron, Midbrain, Neurotransmitter, Mouse, Neurogenesis, Ventral tegmental area (VTA), Serotonin, Dorsal raphe, Rhombomere 1

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