Evolution and expression of D2 and D3 dopamine receptor genes in zebrafish

Abstract

We mined the zebrafish genomic sequence database and identified contigs containing segments of several dopamine receptor genes. By using a polymerase chain reaction amplification strategy, we generated full-length cDNAs encoding a single dopamine D3 receptor and three distinct D2 receptor subtypes. Zebrafish dopamine receptor genes were mapped by using the T51 radiation hybrid panel. The D3 receptor gene (drd3) mapped to linkage group (LG) 24. The three D2 receptor genes were localized to LG 15 (drd2a), LG 16, (drd2b), and LG 5 (drd2c). With the exception of the drd2b gene, each of these map positions was syntenic with regions of human chromosomes containing orthologs of the zebrafish dopamine receptor genes. Whole-mount in situ hybridization was used to investigate expression of the D2 and D3 receptor genes. Expression of the drd3 gene was first detected at mid-somitogenesis and was particularly prominent in somites. Thereafter, the drd3 gene was expressed diffusely throughout the brain and spinal cord. The three D2 receptor genes were expressed throughout the central nervous system (CNS) in distinct but overlapping patterns. In early embryos, the drd2a gene was expressed exclusively in the epiphysis, whereas the drd2c gene was localized to the notochord. After 24 hpf, the drd2a, drd2b, and drd2c genes were differentially expressed throughout the CNS. The identification of dopamine receptor genes in zebrafish should allow us to use the power of zebrafish genetics to analyze the functional properties of this important class of neurotransmitter receptors.

Cloning and spatial and temporal expression of the zebrafish dopamine D1 receptor

“…Topographically, the patterns of drd1 expression are similar to the expression of dopamine transporters (Holzschuh et al, 2001), tyrosine hydroxylase (Guo et al, 1999(Guo et al, , 2000Holzschuh et al, 2001;Gao et al, 2005), and dopamine D2 receptors (Boehmler et al, 2004). However, the onset time of drd1 expression appeared to be delayed several hours compared with the expression of other dopaminergic system-specific genes.…”

“…Recently, the zebrafish (Danio rerio) has emerged as a model vertebrate for molecular and genetic studies of the dopaminergic system (Guo et al, 1999(Guo et al, , 2000Holzschuh et al, 2001;Ma and Lopez, 2003;Boehmler et al, 2004;Gao et al, 2005). By screening the F3 generation of chemically mutagenized zebrafish, for example, Guo et al (1999Guo et al ( , 2000 isolated a large number of gene mutations that disrupt the development or function of the dopaminergic system.…”

“…By screening the F3 generation of chemically mutagenized zebrafish, for example, Guo et al (1999Guo et al ( , 2000 isolated a large number of gene mutations that disrupt the development or function of the dopaminergic system. In addition, some of the key elements involved in dopaminergic signaling have been characterized, including spatial and temporal expression of tyrosine hydroxylase, dopamine transporters (Holzschuh et al, 2001), and D2 receptors (Boehmler et al, 2004). However, molecular studies of dopamine D1 receptors have not been described.…”

Dopamine D2Receptor Activity Modulates Akt Signaling and Alters GABAergic Neuron Development and Motor Behavior in Zebrafish Larvae

“…Several components of the DA biosynthetic and signaling pathways are expressed in the zebrafish larval brain (Holzschuh et al, 2001;Boehmler et al, 2004Boehmler et al, , 2007McLean and Fetcho, 2004;Anichtchik et al, 2006;Li et al, 2007), but which intracellular pathways are modulated by DA and its role in mediating behavior, as well as how DA signaling regulates zebrafish brain development, is not well characterized. Previous studies have demonstrated that DA is involved in larval motor regulation and that this is mediated, in part, by cAMP signaling (Boehmler et al, 2007;Thirumalai and Cline, 2008).…”

“…Orthologous DA D 1 -like and D 2 -like receptor expression is detected in specific embryonic and early larval brain regions (Boehmler et al, 2004(Boehmler et al, , 2007Li et al, 2007). Furthermore, behavioral studies indicate that the neural cells are competent to respond to DA signaling at a time when simple motor behaviors are emerging in the young larvae (Boehmler et al, 2007;Bretaud et al, 2007;Thirumalai and Cline, 2008).…”