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Title: Function of the forkhead gene fd3F in Drosophila chordotonal neuron differentiation
Author: Newton, Fay Gabrielle
ISNI:       0000 0004 2726 6327
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2012
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Drosophila chordotonal (Ch) organs are internal stretch receptors required for coordination, balance and hearing. The outer dendritic segment of the Ch neuron is a compartmentalised motile cilium, a feature that is exclusive to this neuron subtype. Ch organs are specified early in development by expression of the proneural gene atonal in the proneural cluster and sense organ precursors (SOPs) (Jarman et al., 1993). However little is known about how chordotonal SOP specification is linked to differentiation of Ch organs. fd3F encodes a forkhead transcription factor which has been identified as a potential downstream target of atonal in microarray experiments (Cachero et al., 2011). I have shown that fd3F is exclusively expressed in Ch neurons and their precursors in Drosophila embryos and Ch SOPs in larval imaginal discs. I have also generated an fd3F deletion mutant by imprecise excision of a P element. Mutant adults and larvae exhibit impaired coordination characteristic of Ch neuron defects and a similar phenotype was observed in fd3F RNAi lines. fd3F mutant Ch neurons do not show gross morphological defects, however the tips of the Ch neuron cilia appear swollen when analysed by electron microscopy and there is also some mis-localisation of proteins within the cilia. I have identified several Ch-specific genes that show strongly reduced mRNA expression in fd3F mutant embryos compared with wild type and could therefore be downstream targets of fd3F. These include a number of genes known to be essential for Ch neuron function such as transient receptor potential (TRP) ion channels, dyneins required for motility of the Ch neuron cilium and components of the retrograde transport machinery that may be required for protein localisation within the cilium. In addition several uncharacterised genes were identified as fd3F targets and these genes may therefore also be important for Ch neuron function. I have shown that fd3F directly regulates two of these genes, nanchung and inactive using GFP enhancer constructs and gel retardation assays. I therefore hypothesise that fd3F is an important component of the gene regulatory network that links atonal expression in SOPs to differentiation of Ch organs. In particular fd3F regulates genes required specifically for Ch neuron function and enhances expression of retrograde transport genes that may be required to ensure correct distribution of proteins within the compartmentalised Ch neuron cilium.
Supervisor: Jarman, Andrew. ; Armstrong, Douglas. Sponsor: Biotechnology and Biological Sciences Research Council (BBSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: drosophila ; transcription ; neurogenesis ; ciliogenesis