Genetics in Invertebrates: Modeling Dopaminergic Signaling and Neurodegeneration
J. Andrew Hardaway
Neuroscience Graduate Program, Vanderbilt University School of Medicine, U1205 Medical Center North, Nashville, TN 37232, USA.
Correspondence e-mail: firstname.lastname@example.org
Abstract | Dopamine (DA) is an important modulatory neurotransmitter, mediating complex human processes such as arousal, learning, reward and motor control; those same behaviors that go awry in neural disorders such as attention-deficit-hyperactivity disorder(ADHD), bipolar disorder, schizophrenia and Parkinson’s Disease (PD). Owing to the anatomical and genetic complexity of vertebrate model systems, the invertebrate model systems Caenhorhabditis elegans and Drosophila melanogaster are ideal systems to study genetic contributions within DA networks and, in the case of flies, genes that contribute to or suppress DA neuron degeneration. In worms, the use of forward and reverse genetics has revealed how a modest dopaminergic nervous system can regulate locomotion, and how a simple locomotory phenotype can be employed to identify novel regulatory genes and their functions within its DA network. Continued genetic study of these networks may reveal novel genes involved in regulating DA biosynthesis, release, uptake and signaling. Many genes have been identified in familial-associated PD (FAPD), and these candidate genes have been used in flies to study neurodegeneration. This review will describe how flies have been employed to dissect the function of three FAPD genes: α-synuclein, parkin, and PINK1. In the case of parkin and PINK1, reverse genetic approaches in the fly have revealed the importance of mitochondrial dynamics to DA neuron susceptibility in PD. The impact of these findings may define a true departure from classical forward and reverse genetics in invertebrates, and that a clearer understanding of DA neural networks will be revealed through the mutual employment of both with convergent genetics.