robo2 and robo3 interact with eagle to regulate serotonergic neuron differentiation
robo2 and robo3 interact with eagle to regulate serotonergic neuron differentiation
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DOI：
10.1242/dev.00962
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发表时间：
2004-03-01
期刊：
影响因子：
4.6
通讯作者：
Condron, BG
中科院分区：
文献类型：
--
作者：
Couch, JA;Chen, J;Condron, BG
中枢神经系统（CNS）的功能关键取决于神经元的正确分化以及轴突连接的形成。已知神经元分化的某些方面在轴突连接形成时发生。尽管血清素是一种高度保守的神经递质，对许多中枢神经系统功能都很重要，但对血清素能神经元分化的过程知之甚少。我们发现，在果蝇中，血清素转运体（SerT）的表达在时间和空间上都与中线交叉相关。此外，我们表明轴突导向分子roundabout2和roundabout3（robo2/3）对血清素能神经元的分化是必需的，并且其作用独立于它们的配体slit。robo2或robo3的缺失会导致约一半神经元中SerT表达缺失，并且类似于转录因子eagle（eg）突变体中所见的表型。最后，我们展示了robo2/3和eg之间的直接关系：robo2/3突变体在血清素能神经元中失去Eg表达，并且robo2和eg在基因上相互作用以调节SerT表达。我们提出，Robo2/3在中线后的表达是调节血清素能神经元分化的信号的一部分，并由转录因子Eg转导。
The function of the central nervous system (CNS) depends crucially upon the correct differentiation of neurons and formation of axonal connections. Some aspects of neuronal differentiation are known to occur as axonal connections are forming. Although serotonin is a highly conserved neurotransmitter that is important for many CNS functions, little is known about the process of serotonergic neuron differentiation. We show that in Drosophila, expression of the serotonin transporter (SerT) is both temporally and physically related to midline crossing. Additionally, we show that the axon guidance molecules roundabout2 and roundabout3 (robo2/3) are necessary for serotonergic neuron differentiation and function independently of their ligand, slit. Loss of robo2 or robo3 causes a loss of SerT expression in about half of neurons, and resembles the phenotype seen in mutants for the transcription factor eagle (eg). Finally, we show a direct relationship between robo2/3 and eg: robo2/3 mutants lose Eg expression in serotonergic neurons, and robo2 and eg interact genetically to regulate SerT expression. We propose that post-midline expression of Robo2/3 is part of a signal that regulates serotonergic neuron differentiation and is transduced by the transcription factor Eg.