Fay G. Newton's research while affiliated with The University of Edinburgh and other places

Publications (37)

Article
Full-text available
The Drosophila chordotonal neuron cilium is the site of mechanosensory transduction. The cilium has a 9 + 0 axoneme structure and is highly sub-compartmentalised, with proximal and distal zones harbouring different TRP channels and the proximal zone axoneme also being decorated with axonemal dynein motor complexes. The activity of the dynein comple...
Preprint
The Drosophila chordotonal neuron cilium is the site of mechanosensory transduction. The cilium has a 9+0 axoneme structure and is highly sub-compartmentalised, with proximal and distal zones harbouring different TRP channels and the proximal zone axoneme also being decorated with axonemal dynein motor complexes. The activity of the dynein complexe...
Article
Full-text available
Retinitis pigmentosa (RP) is the most common cause of inherited blindness and is characterised by the progressive loss of retinal photoreceptors. However, RP is a highly heterogeneous disease and, while much progress has been made in developing gene replacement and gene editing treatments for RP, it is also necessary to develop treatments that are...
Article
Full-text available
Age-related hearing loss (ARHL) is a threat to future human wellbeing. Multiple factors contributing to the terminal auditory decline have been identified; but a unified understanding of ARHL - or the homeostatic maintenance of hearing before its breakdown - is missing. We here present an in-depth analysis of homeostasis and ageing in the antennal...
Article
Full-text available
The motile cilium/flagellum is an ancient eukaryotic organelle. The molecular machinery of ciliary motility comprises a variety of cilium-specific dynein motor complexes along with other complexes that regulate their activity. Assembling the motors requires the function of dedicated “assembly factors” and transport processes. In humans, mutation of...
Article
Full-text available
In contrast to the progress in understanding ciliogenesis and cilium function, we know less about the transcrip-tional regulation of ciliogenesis genes and how this regulatory program is modulated to generate diverse cilia. Drosophila sensory neurons have ciliary dendrites that are structurally and functionally specialised for receiving different s...
Article
Full-text available
Cilia have evolved hugely diverse structures and functions to participate in a wide variety of developmental and physiological processes. Ciliary specialization requires differences in gene expression, but few transcription factors are known to regulate this, and their molecular function is unclear. Here, we show that the Drosophila Forkhead box (F...
Article
Full-text available
In neurogenesis, neural cell fate specification is generally triggered by proneural transcription factors. Whilst the role of proneural factors in fate specification is well studied, the link between neural specification and the cellular pathways that ultimately must be activated to construct specialised neurons is usually obscure. High-resolution...
Data
Analysis of ato -correlated genes for over-represented protein domains. (0.04 MB DOC)
Data
FACS analysis of cells dissociated from time collections of embryos. Shown are the regions harvested for atoGFP+ and atoGFP− cell samples and the percentage of cells in each area. (A) atoGFP embryos. (B) Non-GFP-expressing wild type embryos (Oregon R). (C) Embryos expressing GFP ubiquitously (ubiGFP). (0.42 MB TIF)
Data
Representation of genes containing selected protein domains. Transcription factor domains (such as the homeodomain, T-box, zinc-finger) are well represented at all time points, whereas domains associated with differentiation increase with time. The TPR domain is strongly associated with genes involved in Golgi trafficking and IFT. All domain counts...
Data
Potential ato target genes based on genes differentially represented in wild-type versus ato-mutant cells. This table shows a subset of the genes in Table S11, selected based on the following additional criterion: ≥2-fold ratio between wild-type and mutant fold-change values (Wt/mut). Compared with the genes in Table S11, this list removes many gen...
Data
Comparison with proneural cluster-expressed genes from a previous profiling analysis. (0.03 MB DOC)
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ato-correlated genes at t3 that have been associated with cilia and/or basal body formation or function and/or are associated with an X box motif. Genes are sorted by overall rank fold-enrichment in atoGFP cells versus the rest of the embryo (>1.5-fold enriched; 1% FDR). (0.20 MB DOC)
Data
Resampling analysis shows that ato-correlated genes are highly enriched for nearby RFX binding motifs (X boxes) at each time point. In each case, significantly enriched genes (≥2-fold, 1% FDR) were selected and their 1-kb upstream sequences analysed for X box sequence matches. To sample the background distribution of such matches, random gene lists...
Data
Expression patterns of ato-correlated genes. A summary of patterns observed from in situ hybridization carried out for this study. (0.10 MB DOC)
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Oligonucleotides used for generation of in situ hybridisation probes, GFP reporter constructs, and gel retardation assays. (0.08 MB DOC)
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Over-representation of PNS-related GO terms in the enriched GO term lists (Tables S4, S5, S6). In this table, the enrichment factor represents the enrichment in PNS-related GO terms relative to similar sized random lists of genes as generated by bootstrap analysis: PNS related GO terms associated with random gene lists were retrieved. This process...
Data
Top 100 ato-correlated genes at time point t2. A list of genes ranked by fold change (FC) (i.e., ratio of expression in atoGFP cells versus the rest of the embryo) (1% FDR). (0.19 MB DOC)
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Functional gene annotation (GO analysis). (0.04 MB DOC)
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Functional gene annotation analysis of genes that are over-represented at t1 in atoGFP cells in wild type embryos. Significance is quantified by the corrected Fisher exact statistic [52]. Only the 50 most significant terms are shown. ‘PNS related’ refers to GO terms that include genes already known to be associated with PNS development. This inform...
Data
Developmental progression in GO term over-representation. (0.03 MB DOC)
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Top 100 ato-correlated genes at time point t1. A list of genes ranked by fold change (FC) (i.e., ratio of expression in atoGFP cells versus the rest of the embryo) (1% FDR). (0.19 MB DOC)
Data
In vitro DNA-binding analysis of EATO motifs from Rfx and dila enhancers. A gel retardation assay showing the binding of ATO/DA heterodimers to oligonucleotide probes containing EATO motifs from the RfxA enhancer (Rfx-EATO1) and dila enhancer (dila-EATO1 and dila-EATO2). Arrow indicates the protein-DNA complexes and arrowhead indicates the free pro...
Data
Over-represented protein domains for combined data from t1–t3. Shown are Pfam domains that are significantly over-represented among genes at any of the three time points (p<0.05 for enrichment in a particular time point), along with the genes in each family. Based on 1.5-fold over-expressed genes, 1% FDR. (0.05 MB DOC)
Data
Functional gene annotation analysis of genes that are over-represented at t3 in atoGFP cells in wild type embryos. Significance is quantified by the corrected Fisher exact statistic [52]. Only the 50 most significant terms are shown. ‘PNS related’ refers to GO terms that include genes already known to be associated with PNS development. This inform...
Data
Functional gene annotation analysis of genes that are over-represented at t2 in atoGFP cells in wild type embryos. Significance is quantified by the corrected Fisher exact statistic [52]. Only the 50 most significant terms are shown. ‘PNS related’ refers to GO terms that include genes already known to be associated with PNS development. This inform...
Data
Top 100 ato-correlated genes at time point t3. A list of genes ranked by fold change (FC) (i.e., ratio of expression in atoGFP cells versus the rest of the embryo) (1% FDR). (0.18 MB DOC)
Data
Genes differentially expressed at t1 in atoGFP cells from wild-type but not in ato mutant embryos. A table of genes that meet the following criteria: ≥2-fold differentially expressed in atoGFP cells from wild-type embryos (fc = ratio of expression in atoGFP cells versus the rest of the embryo) and <2-fold differentially expressed in atoGFP cells fr...
Data
mRNA in situ hybridisation patterns of Ch differentially expressed genes. (A) Pan-neural genes—expressed in both PNS and CNS cells. (B) Pan-sensory genes—expressed in PNS cells only. (C) Ch-enriched genes—expressed initially in Ch precursors, then all sensory lineages (CH and ES), and finally often persisting in Ch neurons only. (D) Ch-specific—exp...
Data
FACS isolation of ato GFP cells and validation. (0.04 MB DOC)

Citations

... {y t7.7 = nos-phiC31\int.NLS}X; P{y t7.7 = CaryP}attP40 (#79604) and w*; P{UASp-Venus.GAP43}7 (#30897). Dnali1-mVenus, Dnal1-mVenus are described in Xiang et al. (2022). Flies with UAS-int attp40 landing site were obtained from the Cambridge Microinjection facility. ...
... II. Retinitis pigmentosa According to the US National Library of Medicine, retinitis pigmentosa is a hereditary condition that affects up to one in every 4,000 persons in the United States and Europe [9]. Due to the slow disintegration of retinal cells, people with this eye disorder frequently have problems seeing at night and lose peripheral vision. ...
... The complex correlation of multiple physiological deficits with hearing loss appears to have mistakenly led to the cause being assumed to the most consistent deficit-for instance with age-related hearing loss being due to the most common stria vascularis pathology (Ramadan and Schuknecht, 1989;Wu et al., 2020). In At present, high-powered quantification of multiple physiological deficits in one model organism in response to noise or age over the course of its lifespan are rare (Keder et al., 2020). Further to this, agerelated hearing loss and noise-induced hearing loss are thought to be very distinct processes (Yang et al., 2015), which could be independent of each other (Corso et al., 1976). ...
... To follow IDA complex localisation, we used an mVenus fusion reporter for Dnali1, hereafter referred to as IDA-Dnali1 for clarity 27 . This is a predicted light-intermediate chain subunit of several monomeric IDA species 14 (Table 1). The corresponding Chlamydomonas subunit (p28) is required for cytoplasmic IDA complex pre-assembly and so IDA complexes do not localise in its absence. ...
... To analyse protein localisation, we made extensive use of transgenic lines expressing the gene of interest (upstream, promoter and coding regions) fused to GFP, mVenus or mCherry reporters. In common with other motile ciliary genes in Drosophila, a relatively small proportion of upstream region drives chordotonal neuron expression through regulation by Rfx and Fd3F transcription factors 25 . We focussed on the differentiating chordotonal neurons of Johnston's Organ within the pupal antenna. ...
... In Drosophila, two genes belong to this class, fd3F and Crg-1 (Fig 1 and S1 Fig). fd3F is first expressed ubiquitously, but from stage 12 onwards expression is exclusively in cell clusters along the ventral and lateral side of the embryo [14,63,196]. These cell clusters correspond to chordotonal (Ch) sensory organs and their precursors, and it has been shown that fd3F regulates specification of this group of ciliated neurons, while the other group of ciliated neurons, the external sensory (ES) neurons, do not express fd3F [63,196]. ...