title: Differentiation and molecular heterogeneity of inhibitory and excitatory neurons associated with midbrain dopaminergic nuclei.
abstract: Local inhibitory GABAergic and excitatory glutamatergic neurons are important for midbrain dopaminergic and hindbrain serotonergic pathways controlling motivation, mood, and voluntary movements. Such neurons reside both within the dopaminergic nuclei, and in adjacent brain structures, including the rostromedial and laterodorsal tegmental nuclei. Compared with the monoaminergic neurons, the development, heterogeneity, and molecular characteristics of these regulatory neurons are poorly understood. We show here that different GABAergic and glutamatergic subgroups associated with the monoaminergic nuclei express specific transcription factors. These neurons share common origins in the ventrolateral rhombomere 1, where the postmitotic selector genes Tal1, Gata2 and Gata3 control the balance between the generation of inhibitory and excitatory neurons. In the absence of Tal1, or both Gata2 and Gata3, the GABAergic precursors adopt glutamatergic fates and populate the glutamatergic nuclei in excessive numbers. Together, our results uncover developmental regulatory mechanisms, molecular characteristics, and heterogeneity of central regulators of monoaminergic circuits.
authors.affiliation: Department of Biosciences, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Lahti
authors.affiliation: Department of Biosciences, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Maarja
authors.initials: M
authors.lastname: Haugas
authors.affiliation: Department of Biosciences, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Tikker
authors.affiliation: Institute of Biotechnology, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Airavaara
authors.affiliation: Institute of Biotechnology, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Merja H
authors.initials: MH
authors.lastname: Voutilainen
authors.affiliation: Institute of Biotechnology, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Anttila
authors.affiliation: Department of Biosciences, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Suman
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Biosciences, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Caisa
authors.initials: C
authors.lastname: Inkinen
authors.affiliation: Department of Veterinary Biosciences, P.O. Box 66, Agnes Sjöbergin katu 2, FIN-00014 University of Helsinki, Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Salminen
authors.affiliation: Department of Biosciences, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland juha.m.partanen@helsinki.fi.
authors.forename: Juha
authors.initials: J
authors.lastname: Partanen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D002645:Chickens; D059290:Dopaminergic Neurons / Q000166:cytology*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D059330:GABAergic Neurons / Q000166:cytology; D050980:GATA Transcription Factors / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000166:cytology*; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008938:Mitosis; D008954:Models, Biological; D009433:Neural Inhibition; D012097:Repressor Proteins / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology; D017557:Ventral Tegmental Area / Q000166:cytology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D050980:GATA Transcription Factors; D005971:Glutamates; D012097:Repressor Proteins; D012701:Serotonin; D005680:gamma-Aminobutyric Acid
keywords: Chicken; Dopamine; GABA; Gata2; Gata3; Glutamate; Hindbrain; Midbrain; Mouse; Neurogenesis; RMTg; SNpr; Serotonin; Tal1; Transcription factor; VTA