Characterization of FKH-8 as a Critical Regulator of Dopaminergic Neuron Function in C. elegans

Full Abstract

Dopaminergic neurons are specialized cells in the brain that produce the neurotransmitter dopamine. This neurotransmitter is important for many functions in humans and other animals, including sleep, mood, learning and movement. In order for dopaminergic neurons to function properly, they must commit to a cell fate and express precise levels of genes encoding signaling molecules and receptors for their response to stimuli. The choices neurons make to become specific neuron type and express certain molecules is thought to be largely controlled by transcription factors, but only a handful of the factors are known. We have recently identified a likely role for a member of the conserved and developmentally important forkhead transcription factor family, fkh-8, in regulating the function of dopaminergic neurons. We have preliminary data that deletion mutants of fkh-8, which is expressed in dopaminergic neurons, exhibit a swimming-induced paralysis phenotype indicative of altered levels of dopamine transport or production. To test our hypothesis that fkh-8 regulates critical aspects of DA neuron function, I am carrying out pharmacological, genetic, and phenotypic analyses. This is significant because it may be possible to use fkh-8 to help generate a program for dopamine neuron development, which could help with future studies to direct stem cells to a dopaminergic fate. This could potentially prevent or reverse diseases like Parkinson's.

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