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.
Footnotes
Author contributions
J.P. directed the project, analysed data and wrote the manuscript together with M.S.; L.L. designed and performed most of the experiments, analysed data, prepared images, and wrote the manuscript; M.H. and L.T. designed and performed experiments, prepared images, and analysed data; S.K. and C.I. performed experiments and analysed data; M.A., M.H.V. and J.A. designed and performed experiments, including stereotaxic injections, and wrote the manuscript.
Funding
This work was supported by the Academy of Finland (J.P., L.L., M.A., J.A., M.H.V.); Sigrid Juselius Foundation (J.P., M.S.); University of Helsinki (M.H.); Center for International Mobility (CIMO; L.T.); Otto A. Malm foundation (L.T.); Integrative Life Sciences doctoral program (L.T.); Ella and Georg Ehrnrooth Foundation (L.L.); and Jane and Aatos Erkko Foundation (J.P.).
