title: Distinct developmental origins and regulatory mechanisms for GABAergic neurons associated with dopaminergic nuclei in the ventral mesodiencephalic region.
abstract: GABAergic neurons in the ventral mesodiencephalic region are highly important for the function of dopaminergic pathways that regulate multiple aspects of behavior. However, development of these neurons is poorly understood. We recently showed that molecular regulation of differentiation of the GABAergic neurons associated with the dopaminergic nuclei in the ventral midbrain (VTA and SNpr) is distinct from the rest of midbrain, but the reason for this difference remained elusive. Here, we have analyzed the developmental origin of the VTA and SNpr GABAergic neurons by genetic fate mapping. We demonstrate that the majority of these GABAergic neurons originate outside the midbrain, from rhombomere 1, and move into the ventral midbrain only as postmitotic neuronal precursors. We further show that Gata2, Gata3 and Tal1 define a subpopulation of GABAergic precursors in ventral rhombomere 1. A failure in GABAergic neuron differentiation in this region correlates with loss of VTA and SNpr GABAergic neurons in Tal1 mutant mice. In contrast to midbrain, GABAergic neurons of the anterior SNpr in the diencephalon are not derived from the rhombomere 1. These results suggest unique migratory pathways for the precursors of important GABAergic neuron subpopulations, and provide the basis for understanding diversity within midbrain GABAergic neurons.
authors.affiliation: Department of Biosciences, PO Box 56, Viikinkaari 5, FIN00014-University of Helsinki, Helsinki, Finland.
authors.forename: Kaia
authors.initials: K
authors.lastname: Achim
authors.forename: Paula
authors.initials: P
authors.lastname: Peltopuro
authors.forename: Laura
authors.initials: L
authors.lastname: Lahti
authors.forename: James
authors.initials: J
authors.lastname: Li
authors.forename: Marjo
authors.initials: M
authors.lastname: Salminen
authors.forename: Juha
authors.initials: J
authors.lastname: Partanen
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis; D019070:Cell Lineage; D002465:Cell Movement; D059290:Dopaminergic Neurons / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D050989:GATA2 Transcription Factor / Q000032:analysis; D050990:GATA3 Transcription Factor / Q000032:analysis; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000032:analysis; D013378:Substantia Nigra / Q000166:cytology / Q000254:growth & development*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D017557:Ventral Tegmental Area / Q000166:cytology / Q000254:growth & development*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; C489366:Tal1 protein, mouse