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PMID:19088086

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Citation

Kala, K, Haugas, M, Lilleväli, K, Guimera, J, Wurst, W, Salminen, M and Partanen, J (2009) Gata2 is a tissue-specific post-mitotic selector gene for midbrain GABAergic neurons. Development 136:253-62

Abstract

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.

Links

PubMed Online version:10.1242/dev.029900

Keywords

Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors/deficiency; Basic Helix-Loop-Helix Transcription Factors/genetics; Body Patterning/genetics; Cell Differentiation/genetics; Embryonic Stem Cells/cytology; Embryonic Stem Cells/metabolism; Female; GATA2 Transcription Factor/genetics; GATA3 Transcription Factor/genetics; Gene Expression Regulation, Developmental; Male; Mesencephalon/cytology; Mesencephalon/embryology; Mesencephalon/metabolism; Mice; Mice, Knockout; Mice, Mutant Strains; Mice, Transgenic; Mitosis/genetics; Models, Neurological; Neurogenesis/genetics; Neurons/cytology; Neurons/metabolism; Pregnancy; RNA, Messenger/genetics; RNA, Messenger/metabolism; Repressor Proteins/genetics; Tissue Distribution; gamma-Aminobutyric Acid/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GATA2

acts_upstream_of_or_within

GO:0048663: neuron fate commitment

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4818492

P

  • results_in_commitment_to:(CL:0000617)|results_in_commitment_to:(CL:0000617)|results_in_commitment_to:(CL:0000850)

Seeded From UniProt

complete


See also

References

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