Tsalik Ephraim L, Niacaris Timothy, Wenick Adam S, Pau Kelvin, Avery Leon, Hobert Oliver
Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Dev Biol. 2003 Nov 1;263(1):81-102. doi: 10.1016/s0012-1606(03)00447-0.
Biogenic amines regulate a variety of behaviors. Their functions are predominantly mediated through G-protein-coupled 7-transmembrane domain receptors (GPCR), 16 of which are predicted to exist in the genome sequence of the nematode Caenorhabditis elegans. We describe here the expression pattern of several of these aminergic receptors, including two serotonin receptors (ser-1 and ser-4), one tyramine receptor (ser-2), and two dopamine receptors (dop-1 and dop-2). Moreover, we describe distinct but partially overlapping expression patterns of different splice forms of the ser-2 tyramine receptor locus. We find that each of the aminergic receptor genes is expressed in restricted regions of the nervous system and that many of them reveal significant overlap with the expression of regulatory factors of the LIM homeobox (Lhx) gene family. We demonstrate that the expression of several of the biogenic amine receptors is abrogated in specific cell types in Lhx gene mutants, thus establishing a role for these Lhx genes in regulating aspects of neurotransmission. We extend these findings with other cell fate markers and show that the lim-4 Lhx gene is required for several but not all aspects of RID motor neuron differentiation and that the lim-6 Lhx gene is required for specific aspects of RIS interneuron differentiation. We also use aminergic receptor gfp reporter fusions as tools to visualize the anatomy of specific neurons in Lhx mutant backgrounds and find that the development of the elaborate dendritic branching pattern of the PVD harsh touch sensory neuron requires the mec-3 Lhx gene. Lastly, we analyze a mutant allele of the ser-2 tyramine receptor, a target of the ttx-3 Lhx gene in the AIY interneuron class. ser-2 mutants display none of the defects previously shown to be associated with loss of AIY function.
生物胺调节多种行为。它们的功能主要通过G蛋白偶联的7跨膜结构域受体（GPCR）介导，其中16种预计存在于线虫秀丽隐杆线虫的基因组序列中。我们在此描述了其中几种胺能受体的表达模式，包括两种5-羟色胺受体（ser-1和ser-4）、一种酪胺受体（ser-2）和两种多巴胺受体（dop-1和dop-2）。此外，我们描述了ser-2酪胺受体基因座不同剪接形式的独特但部分重叠的表达模式。我们发现每个胺能受体基因都在神经系统的特定区域表达，并且其中许多与LIM同源盒（Lhx）基因家族调节因子的表达有显著重叠。我们证明，在Lhx基因突变体的特定细胞类型中，几种生物胺受体的表达被消除，从而确立了这些Lhx基因在调节神经传递方面的作用。我们用其他细胞命运标记扩展了这些发现，表明lim-4 Lhx基因是RID运动神经元分化的几个但不是所有方面所必需的，而lim-6 Lhx基因是RIS中间神经元分化特定方面所必需的。我们还使用胺能受体gfp报告基因融合作为工具，在Lhx突变背景下可视化特定神经元的解剖结构，发现PVD强触觉感觉神经元精细树突分支模式的发育需要mec-3 Lhx基因。最后，我们分析了ser-2酪胺受体的一个突变等位基因，它是AIY中间神经元类中ttx-3 Lhx基因的一个靶点。ser-2突变体没有表现出先前显示与AIY功能丧失相关的任何缺陷。
