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Start date: 2020Subject: search.filters.subject.development

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    N-terminal oligomerization drives HDAC4 nuclear condensation and neurodevelopmental dysfunction in Drosophila
    (The Royal Society, 2025-10) Hawley HR; Sutherland-Smith AJ; Savoian MS; Fitzsimons HL
    Histone deacetylase four (HDAC4) undergoes dynamic nucleocytoplasmic shuttling, a process critical for regulating its activity. However, aberrant nuclear accumulation of HDAC4 is associated with both neurodevelopmental and neurodegenerative disease, and in our Drosophila model, impairs normal neuronal development. Upon nuclear accumulation, HDAC4 forms biomolecular condensates, previously termed aggregates, that correlate with the severity of defects in development of the Drosophila mushroom body and adult eye. Here we determined that nuclear condensation of HDAC4 is dependent on self-oligomerization, and that impairing oligomerization reduces condensation and the severity of neurodevelopmental phenotypes in Drosophila. HDAC4 condensates are highly dynamic and are stabilized by the presence of MEF2, which promotes their formation, ultimately exacerbating phenotypic severity. These data provide insight into the role of HDAC4 condensates in normal neuronal function and suggest that their dysregulation may contribute to neurodevelopmental disorders. Consequently, targeting oligomerization of HDAC4 and its interaction with MEF2 present potential therapeutic strategies for diseases associated with HDAC4 nuclear accumulation.
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    Characterising CG5846 (Peep) in Drosophila melanogaster neural function : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Biochemistry at Massey University, Manawatū, New Zealand
    (Massey University, 2024) Wilson, Sarah Jean
    Histone deacetylase 4 (HDAC4) is a transcriptional regulator that has been implicated in a number of neurodevelopmental and neurodegenerative diseases that are associated with intellectual disability, cognitive defects, and/or memory loss. Both the accumulation of nuclear HDAC4 and its loss-of-function have been linked to these conditions, therefore exploring HDAC4’s role in neuronal function is essential to understand the molecular mechanisms underlying these diseases. In Drosophila, overexpression of HDAC4 results in defects in morphogenesis of axons in the mushroom body, a structure essential for memory formation, as well as long-term memory defects and disruption to the development of the compound eye. The molecular mechanisms underlying these HDAC4-induced phenotypes are currently unknown. RNA-sequencing on fly heads in which HDAC4 was overexpressed has previously been performed and showed few genes were transcriptionally regulated by HDAC4. In addition, an enhancer/suppressor rough eye phenotype screen has also been performed which identified a number of genes that interact genetically in the same molecular pathway as HDAC4. To further investigate the molecular mechanisms underlying HDAC4 dysfunction, an RNA interference (RNAi) based candidate screen for potential HDAC4-interactors was performed, which involved quantification of developmental defects in the mushroom body and eye following RNAi knockdown of each candidate. It was hypothesised that if a phenotype resulting from RNAi knockdown was similar to that induced by HDAC4 overexpression, that candidate may function in similar molecular pathways. A single candidate-interactor was selected (CG5846, named Peep) for further investigation. On overexpression, Peep and HDAC4 co- distribute in nuclei of mushroom body neurons, however no physical interaction was detected. Furthermore, overexpression of Peep did not rescue the HDAC4-induced mushroom body or eye defects. Due to the uncharacterised nature of Peep, a thorough investigation was performed to assess the importance of Peep in survival, longevity, motor function, brain development, courtship learning and memory, and wing development. Peep was observed to be essential for survival of glial cells and for normal mushroom body development, which warrants further investigation. Reduced expression of Peep also resulted in a unique severe necrotic eye phenotype, and through this, Peep was shown to play a potential role in processes involved in regulating mitochondrial and proteasomal function, apoptosis and oxidative stress. These data provide the first documented characterisation of the functional role of Peep in Drosophila development and provide the basis for further investigation into the underlying molecular mechanisms involved in mushroom body and eye development.
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    International development and tourism geographies
    (Taylor and Francis Group, 2024-03-19) Scheyvens R
    This commentary reviews the state of tourism and international development scholarship with special attention to publications from this journal, Tourism Geographies. Rather than assuming that tourism is the end game, or goal, as a body of researchers tourism geographers have often identified concerns about the exploitative impacts of tourism development on low income communities and countries, and negative environmental implications, especially when tourism is externally-driven. However, many of us have also asked, ‘can tourism contribute effectively to international development, and if so, how?’. The articles resulting from this line of research focus on a range of approaches, from sustainable tourism through to inclusive and regenerative tourism, which show that there are ways in which tourism can facilitate rather than impede development. In a neoliberal-dominant world facing significant challenges including climate change, structural inequalities and complex conflicts, it is more important than ever that we keep this question–can tourism contribute to development and if so, how? - central to our research. After providing a concise history of research in this field, this article will discuss the value of some recent trends in tourism scholarship, as well as identifying research gaps and pointing to future directions for research by tourism geographers.
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    Developmentally controlled changes during Arabidopsis leaf development indicate causes for loss of stress tolerance with age
    (Oxford University Press on behalf of the Society for Experimental Biology, 2020-10-22) Kanojia A; Gupta S; Benina M; Fernie AR; Mueller-Roeber B; Gechev T; Dijkwel PP; Foyer C
    Leaf senescence is the final stage of leaf development and is induced by the gradual occurrence of age-related changes (ARCs). The process of leaf senescence has been well described, but the cellular events leading to this process are still poorly understood. By analysis of progressively ageing, but not yet senescing, Arabidopsis thaliana rosette leaves, we aimed to better understand processes occurring prior to the onset of senescence. Using gene expression analysis, we found that as leaves mature, genes responding to oxidative stress and genes involved in stress hormone biosynthesis and signalling were up-regulated. A decrease in primary metabolites that provide protection against oxidative stress was a possible explanation for the increased stress signature. The gene expression and metabolomics changes occurred concomitantly to a decrease in drought, salinity, and dark stress tolerance of individual leaves. Importantly, stress-related genes showed elevated expression in the early ageing mutant old5 and decreased expression in the delayed ageing mutant ore9. We propose that the decreased stress tolerance with age results from the occurrence of senescence-inducing ARCs that is integrated into the leaf developmental programme, and that this ensures a timely and certain death.