Identification of a Dopaminergic Enhancer Indicates Complexity in Vertebrate Dopamine Neuron Phenotype Specification
- Fujimoto, E., Stevenson, T.J., Chien, C.B., and Bonkowsky, J.L.
- Developmental Biology 352(2): 393-404 (Journal)
- Registered Authors
- Bonkowsky, Joshua, Chien, Chi-Bin, Fujimoto, Esther
- Dopamine, Enhancers, Zebrafish, CNS, Basal ganglia
- MeSH Terms
- Animals, Genetically Modified
- Enhancer Elements, Genetic*
- Gene Expression Regulation, Developmental
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Models, Neurological
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism
- 21276790 Full text @ Dev. Biol.
Fujimoto, E., Stevenson, T.J., Chien, C.B., and Bonkowsky, J.L. (2011) Identification of a Dopaminergic Enhancer Indicates Complexity in Vertebrate Dopamine Neuron Phenotype Specification. Developmental Biology. 352(2):393-404.
The dopaminergic neurons of the basal ganglia play critical roles in CNS function and human disease, but specification of dopamine neuron phenotype is poorly understood in vertebrates. We performed an in vivo screen in zebrafish to identify dopaminergic neuron enhancers, in order to facilitate studies on the specification of neuronal identity, connectivity, and function in the basal ganglia. Based primarily on identification of conserved non-coding elements, we tested 54 DNA elements from four species (zebrafish, pufferfish, mouse, and rat), that included 21 genes with known or putative roles in dopaminergic neuron specification or function. Most elements failed to drive CNS expression or did not express specifically in dopaminergic neurons. However, we did isolate a discrete enhancer from the otpb gene that drove specific expression in diencephalic dopaminergic neurons, although it did not share sequence conservation with regulatory regions of otpa or other dopamine-specific genes. For the otpb enhancer, regulation of expression in dopamine neurons requires multiple elements spread across a large genomic area. In addition, we compared our in vivo testing with in silico analysis of genomic regions for genes involved in dopamine neuron function, but failed to find conserved regions that functioned as enhancers. We conclude that regulation of dopaminergic neuron phenotype in vertebrates is regulated by dispersed regulatory elements.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes