Differentiation and molecular heterogeneity of inhibitory and excitatory neurons associated with midbrain dopaminergic nuclei

• DOI: 10.1242/dev.129957
• Publication Date: 2015-12-31T02:43:29Z
• Authors: Laura Lahti; Maarja Haugas; Laura Tikker; Mikko Airavaara; Merja H. Voutilainen; Jenni Anttila; Suman Kumar; Caisa Inkinen; Marjo Salminen; Juha Partanen
• Keywords: Cell Nucleus; Male; Mice, Inbred ICR; 0303 health sciences; Dopaminergic Neurons; Mitosis; Cell Differentiation; Forkhead Transcription Factors; Neural Inhibition; Embryo, Mammalian; GATA Transcription Factors; Models, Biological; Mice, Inbred C57BL; Repressor Proteins; 03 medical and health sciences; Glutamates; Mesencephalon; Animals; Female; GABAergic Neurons; Chickens; Biomarkers

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 to 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 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.