The Transcription Factor FKH-8 is Essential for Dopamine Neuron Function

Faculty #4
Discipline: Biological Sciences
Subcategory: STEM Research

Brian L. Nelms - Fisk University
Co-Author(s): Erica Tross, Bobby Jones, Corey Roach, Ke'Ara Brown-Smith, Bryan Cawthon, and Kai Bracey, Fisk University, Fisk-Vanderbilt Masters-to-PhD Bridge Program

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Dopamine is an important neurotransmitter found throughout the animal kingdom that helps to regulate motor control, cognition, mood, and behavior. Dopamine levels are tightly controlled at multiple steps including dopamine biosynthesis, vesicle packaging, neuron excitability, release, reuptake, and metabolism. While some of the core components of the dopamine signaling pathway are known, we still have much more to learn about transcriptional control of dopamine neuron gene expression. In order to discover and understand new molecules involved in dopamine signaling, we use the model organism C. elegans, which has a simple nervous system that is easily observed and manipulated through both genetic and pharmacological approaches. Our work has identified the transcription factor FKH-8, a member of the highly conserved forkhead family, as an important regulator of dopamine neuron function. FKH-8 is expressed in all dopamine neurons and fkh-8 deletion mutants show an extrasynaptic dopamine-dependent motor defect, swimming-induced paralysis (SWIP), similar to mutants with a deletion of the dopamine transporter gene dat-1. However, the FKH-8 SWIP defect is independent of DAT-1, as dat-1 expression levels are unchanged, and DAT-1 function is intact. We are using genetic and pharmacological approaches to more precisely determine the position of FKH-8 within the dopamine signaling pathway, particularly in dopamine metabolism. We have also performed RNA-Seq from sorted dopamine neurons to identify potential gene targets of FKH-8 and genes that are upregulated in dopamine neurons in general. This strategy is helping us to uncover additional novel regulators of dopamine neuron development, maintenance, and function.

Funder Acknowledgement(s): NSF HBCU-UP Research Initiation Award (Award #HRD14-01091)/NIH R25 “The Fisk-Vanderbilt Biomedical Bridge to the Doctorate” (Award #1R25GM107754-01).

Faculty Advisor: None Listed,