Lahti Laura, Haugas Maarja, Tikker Laura, Airavaara Mikko, Voutilainen Merja H, Anttila Jenni, Kumar Suman, Inkinen Caisa, Salminen Marjo, Partanen Juha
Department of Biosciences, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
Institute of Biotechnology, P.O. Box 56, Viikinkaari 9, FIN-00014 University of Helsinki, Helsinki, Finland.
Development. 2016 Feb 1;143(3):516-29. doi: 10.1242/dev.129957. Epub 2015 Dec 30.
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.
局部抑制性γ-氨基丁酸能神经元和兴奋性谷氨酸能神经元对于中脑多巴胺能和后脑5-羟色胺能通路控制动机、情绪和自主运动至关重要。这类神经元既存在于多巴胺能核团内，也存在于相邻脑结构中，包括嘴内侧和背外侧被盖核。与单胺能神经元相比，这些调节性神经元的发育、异质性和分子特征了解较少。我们在此表明，与单胺能核团相关的不同γ-氨基丁酸能和谷氨酸能亚群表达特定转录因子。这些神经元在腹外侧菱脑节1有共同起源，有丝分裂后选择基因Tal1、Gata2和Gata3在此控制抑制性和兴奋性神经元生成之间的平衡。在缺乏Tal1或Gata2和Gata3两者时，γ-氨基丁酸能前体采用谷氨酸能命运并大量填充谷氨酸能核团。总之，我们的结果揭示了单胺能回路中枢调节因子的发育调节机制、分子特征和异质性。
