Ryu Soojin, Mahler Julia, Acampora Dario, Holzschuh Jochen, Erhardt Simone, Omodei Daniela, Simeone Antonio, Driever Wolfgang
Department of Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.
Curr Biol. 2007 May 15;17(10):873-80. doi: 10.1016/j.cub.2007.04.003. Epub 2007 May 3.
Neurons that produce dopamine as a neurotransmitter constitute a heterogeneous group involved in the control of various behaviors and physiology. In mammals, dopaminergic neurons are found in distinct clusters mainly located in the ventral midbrain and the caudal forebrain [1]. Although much is known about midbrain dopaminergic neurons, development of diencephalic dopaminergic neurons is poorly understood. Here we demonstrate that Orthopedia (Otp) homeodomain protein is essential for the development of specific subsets of diencephalic dopaminergic neurons. Zebrafish embryos lacking Otp activity are devoid of dopaminergic neurons in the hypothalamus and the posterior tuberculum. Similarly, Otp-/- mouse [2, 3] embryos lack diencephalic dopaminergic neurons of the A11 group, which constitutes the diencephalospinal dopaminergic system. In both systems, Otp is expressed in the affected dopaminergic neurons as well as in potential precursor populations, and it might contribute to dopaminergic cell specification and differentiation. In fish, overexpression of Otp can induce ectopic tyrosine hydroxylase and dopamine transporter expression, indicating that Otp can specify aspects of dopaminergic identity. Thus, Otp is one of the few known transcription factors that can determine aspects of the dopaminergic phenotype and the first known factor to control the development of the diencephalospinal dopaminergic system.
产生多巴胺作为神经递质的神经元构成了一个异质性群体，参与各种行为和生理功能的控制。在哺乳动物中，多巴胺能神经元主要位于腹侧中脑和尾侧前脑的不同簇中[1]。尽管对中脑多巴胺能神经元已经有很多了解，但间脑多巴胺能神经元的发育却知之甚少。在这里，我们证明正位蛋白（Otp）同源结构域蛋白对于间脑多巴胺能神经元特定亚群的发育至关重要。缺乏Otp活性的斑马鱼胚胎在下丘脑和后结节中没有多巴胺能神经元。同样，Otp基因敲除小鼠[2,3]胚胎缺乏构成间脑脊髓多巴胺能系统的A11组间脑多巴胺能神经元。在这两个系统中，Otp在受影响的多巴胺能神经元以及潜在的前体细胞群中表达，并且它可能有助于多巴胺能细胞的特化和分化。在鱼类中，Otp的过表达可以诱导异位酪氨酸羟化酶和多巴胺转运体的表达，表明Otp可以确定多巴胺能特性的某些方面。因此，Otp是少数已知的能够决定多巴胺能表型某些方面的转录因子之一，也是第一个已知的控制间脑脊髓多巴胺能系统发育的因子。
