Award: Woodrow Wilson
A Novel Tool for Isoform Specific Knock-down of Tyrosine Hydroxylase in Drosophila
Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the synthesis of dopamine (DA), which is a neurotransmitter essential for regulating behavior. In Drosophila, DA is also required in hypodermal cells as a precursor substrate for cuticle melanization. Alternative splicing produces two isoforms of TH, one which is necessary for the synthesis of DA in the brain and another for peripheral tissues. Existing RNAi lines targeting and suppressing the expression of both isoforms result in lethality, preventing their use in studying the neural function of DA. To address this issue, we generated a miRNA targeted to an exon-exon junction specific to the neural isoform of TH. Behavioral and staining experiments confirm that this novel tool efficiently suppresses the expression of neural TH without causing lethality, providing a useful method to study the function of DA in the central nervous system.
Mentor: Dr. Mark N. Wu, Department of Neurology