Gata2 is a tissue-specific post-mitotic selector gene for midbrain GABAergic neurons.
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.
Kala
Kaia
K
Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
Haugas
Maarja
M
Lilleväli
Kersti
K
Guimera
Jordi
J
Wurst
Wolfgang
W
Salminen
Marjo
M
Partanen
Juha
J
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics*; D050990:GATA3 Transcription Factor / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008938:Mitosis / Q000235:genetics; D008959:Models, Neurological; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D012333:RNA, Messenger; D012097:Repressor Proteins; D005680:gamma-Aminobutyric Acid; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; C487897:Helt protein, mouse