Löhr Heiko, Ryu Soojin, Driever Wolfgang
Developmental Biology, Institute Biology I, Faculty of Biology, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.
Development. 2009 Mar;136(6):1007-17. doi: 10.1242/dev.033878.
Vertebrate dopaminergic neurons develop in distinct neural territories to constitute one of the major neuromodulatory systems. We have identified a zebrafish mutation in the bHLH-PAS family member arnt2, based on a strong reduction in cell number of specific dopaminergic neuron groups in the hypothalamus and posterior tuberculum. Knockdown of sim1 causes a dopaminergic phenotype similar to arnt2 mutants, suggesting that Sim1 acts as a binding partner of Arnt2, similar to their role in hypothalamic neuroendocrine cell specification. sim1, arnt2 and otp are co-expressed in dopaminergic neurons, and combined overexpression of Sim1 and Otp leads to formation of supernumerary dopaminergic neurons in the ventral diencephalon. Arnt2, Sim1 and Otp thus are core components of a conserved transcriptional network, which specifies neuroendocrine as well as A11-related dopaminergic neurons in the fish hypothalamus and posterior tuberculum. Our data suggest a common evolutionary origin of specific hypothalamic neuroendocrine and dopaminergic systems.
脊椎动物的多巴胺能神经元在不同的神经区域发育，构成主要的神经调节系统之一。基于下丘脑和后结节中特定多巴胺能神经元群细胞数量的显著减少，我们在bHLH-PAS家族成员arnt2中鉴定出一种斑马鱼突变。敲低sim1会导致类似于arnt2突变体的多巴胺能表型，这表明Sim1作为Arnt2的结合伴侣发挥作用，类似于它们在下丘脑神经内分泌细胞特化中的作用。sim1、arnt2和otp在多巴胺能神经元中共同表达，Sim1和Otp的联合过表达导致腹侧间脑中超数多巴胺能神经元的形成。因此，Arnt2、Sim1和Otp是一个保守转录网络的核心组成部分，该网络在鱼类下丘脑和后结节中指定神经内分泌以及与A11相关的多巴胺能神经元。我们的数据表明特定下丘脑神经内分泌和多巴胺能系统具有共同的进化起源。
