Discovering signaling mechanisms governing metabolism and metabolic diseases with Drosophila

Kim, Seung K.; Tsao, Deborah D.; Suh, Greg S.B.; Miguel-Aliaga, Irene

doi:10.1016/j.cmet.2021.05.018

Cited by 55 publications

(51 citation statements)

References 176 publications

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“…Insulin signaling regulates the growth of developing tissues by modulating both cell number and size ( Rulifson et al 2002 ; reviewed in Kim et al 2021 ). Measurement of adult wing size has been used to quantify disruption of insulin signaling during Drosophila development ( Park et al 2014 ).…”

Section: Resultsmentioning

confidence: 99%

“…Intersectional binary expression approaches such as simultaneous use of the LexA/LexAop and Gal4/UAS systems have empowered fly biology, particularly in studies of neuroscience, and intercellular communication coordinating metazoan metabolism ( Kim et al 2021 ). For example, simultaneous use of 2 independent binary expression systems allowed clonal analysis of multiple cell populations ( Lai and Lee 2006 ; Bosch et al 2015 ), studies of tissue epistasis ( Yagi et al 2010 ), and elucidation of otherwise undetected contacts between cells ( Gordon and Scott 2009 ; Macpherson et al 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…To investigate the impact of targeted gene suppression, investigators have used Gal4/UAS-mediated gene knockdown to express short hairpin RNAs (shRNAs) in specific cell types ( Ni et al 2011 ). Studies of many biological questions require simultaneous manipulation of 2 or more independent cell populations or genes (reviewed in Kim et al 2021 ). These studies often benefit from multiple binary systems combined in a single fly to study genetic perturbations in multiple tissues.…”

Section: Introductionmentioning

confidence: 99%

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Transgenic Drosophila lines for LexA-dependent gene and growth regulation

Chang

Tsao

Bennett

et al. 2022

G3 Genes|Genomes|Genetics

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Conditional expression of short hairpin RNAs (shRNAs) with binary genetic systems is an indispensable tool for studying gene function. Addressing mechanisms underlying cell-cell communication in vivo benefits from simultaneous use of two independent gene expression systems. To complement the abundance of existing Gal4/UAS-based resources in Drosophila, we and others have developed LexA/LexAop-based genetic tools. Here, we describe experimental and pedagogical advances that promote the efficient conversion of Drosophila Gal4 lines to LexA lines, and the generation of LexAop-shRNA lines to suppress gene function. We developed a CRISPR/Cas9-based knock-in system to replace Gal4 coding sequences with LexA, and a LexAop-based shRNA expression vector to achieve shRNA-mediated gene silencing. We demonstrate the use of these approaches to achieve targeted genetic loss-of-function in multiple tissues. We also detail our development of secondary school curricula that enable students to create transgenic flies, thereby magnifying the production of well-characterized LexA/LexAop lines for the scientific community. The genetic tools and teaching methods presented here provide LexA/LexAop resources that complement existing resources to study intercellular communication coordinating metazoan physiology and development.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transgenic Drosophila lines for LexA-dependent gene and growth regulation

Chang

Tsao

Bennett

et al. 2022

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

show abstract

“…The evolutionary of both cell-intrinsic nutrient-sensing [5,6] and inter-organ energy homeostasis [7][8][9] between flies and mammals are now well-appreciated. In particular, this conservation includes both lipid sensing and its dysregulation, including the development of insulin resistance and 'diabetic' phenotypes [9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nuclear Retention of Leptin/Upd2 Regulates Organismal Resilience to Nutrient Extremes

et al. 2021

Preprint

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Adipocytes release adipokines to function as a systemic ‘adipometer’ and signal satiety. For organisms to function effectively, adipocytes must switch adeptly between adipokine release and retention. We investigated how Unpaired2 (Upd2), a Drosophila ortholog of the human adipokine Leptin, is retained during fasting. Unexpectedly, we find that fasting induces Upd2 nuclear accumulation; and that Upd2 nuclear retention is regulated by Atg8. Atg8 is a ubiquitin like protein which conjugates to a lipid moiety. In fed cells, Atg8 localizes both to the nucleus and the cytoplasm. On fasting Atg8 lipidation levels increase, and the nuclear pool of Atg8 is depleted. We find that Atg8 lipidation is the rate limiting step in Upd2 nuclear exit. Illustrating the physiological significance of Atg8-mediated adipokine nuclear retention, we show that this mechanism promotes starvation resilience and post-fasting hunger. Our findings uncover a new facet of Atg8 biology in regulating context-dependent nuclear export and protein localization.

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Drosophila melanogaster as a dynamic in vivo model organism reveals the hidden effects of interactions between microplastic/nanoplastic and heavy metals

Demir

2022

J of Applied Toxicology

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Plastic waste in different environments has been constantly transforming into microplastic/nanoplastic (MNPLs). As they may coexist with other contaminants, they may behave as vectors that transport various toxic trace elements, including metals.Because the impact of exposure to such matter on health still remains elusive, the abundant presence of MNPLs has lately become a pressing environmental issue.Researchers have been utilizing Drosophila melanogaster as a dynamic in vivo model in genetic research for some time. The fly has also recently gained wider recognition in toxicology and nanogenotoxicity studies. The use of nanoparticles in numerous medical and consumer products raises serious concern, since many in vitro studies have shown their toxic potential. However, there is rather limited in vivo research into nanomaterial genotoxicity using mice or other mammalians owing to high costs and ethical concerns. In this context, Drosophila, thanks to its genetic tractability, short life span, with its entire life cycle lasting about 10 days, and distinct developmental stages, renders this organism an excellent model in testing toxic effects mediated by MNPLs. This review therefore aims to encourage research entities to employ Drosophila as a model in their nanogenotoxicity experiments focusing on impact of MNPLs at the molecular level.

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Discovering signaling mechanisms governing metabolism and metabolic diseases with Drosophila

Cited by 55 publications

References 176 publications

Transgenic Drosophila lines for LexA-dependent gene and growth regulation

Transgenic Drosophila lines for LexA-dependent gene and growth regulation

Nuclear Retention of Leptin/Upd2 Regulates Organismal Resilience to Nutrient Extremes

Drosophila melanogaster as a dynamic in vivo model organism reveals the hidden effects of interactions between microplastic/nanoplastic and heavy metals

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