Transgenic fluorescent zebrafish lines that have revolutionized biomedical research

Choe, Chong Pyo; Choi, Seok‐Yong; Kee, Yun; Kim, Min Jung; Kim, Seok-Hyung; Lee, Yoonsung; Park, Hae-Chul; Ro, Hyunju

doi:10.1186/s42826-021-00103-2

Cited by 45 publications

(27 citation statements)

References 368 publications

(407 reference statements)

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“…The transparency at the larval stage and the availability of reporter lines means that it is possible to isolate cells by flow cytometry or image them at the single cell level in the living organism, opening up opportunities for mechanistic studies in senescence. There are over 8000 transgenic lines with fluorescent reporters, which model specific diseases, label molecules, specific organelles or specific cell types, allowing their visualisation and tracking in vivo [35]. For example there are transgenic lines labelling most cell types of the immune system [36].…”

Section: Discussionmentioning

confidence: 99%

A p21-GFP zebrafish model of senescence for rapid testing of senolyticsin vivo

Morsli

Henriques

Ellis

et al. 2022

Preprint

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Senescence drives the onset and severity of multiple ageing-associated diseases as well as frailty. As a result, there has been an increased interest in mechanistic studies and in the search for compounds targeting senescent cells, known as senolytics. Mammalian models are commonly used to test senolytics and generate functional and toxicity data at the level of organs and systems, yet this is expensive and time consuming. Zebrafish share high homology in genes associated with human ageing and disease. They can be genetically-modified relatively easily. In larvae, most organs develop within 5 days of fertilisation and are transparent, which allows tracking of fluorescent cells in vivo in real time, testing drug off-target toxicity and assessment of cellular and phenotypic changes. Here, we have generated a transgenic zebrafish line that expresses green fluorescent protein (GFP) under the promoter of a key senescence marker, p21. We show an increase in p21:GFP+ cells in larvae following exposure to ionising radiation and with natural ageing. p21:GFP+ cells display other markers of senescence, including senescence-associated β-galactosidase and IL6 The observed increase in senescent cells following irradiation is associated with a reduction in the thickness of muscle fibres and mobility, two important ageing phenotypes. We also show that quercetin and dasatinib, two senolytics currently in clinical trials, reduce the number of p21:GFP+ cells, in a rapid 5-day assay. This model provides an important tool to study senescence in a living organism, allowing the rapid selection of senolytics before moving to more expensive and time-consuming mammalian systems.

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Section: Discussionmentioning

confidence: 99%

A p21-GFP zebrafish model of senescence for rapid testing of senolyticsin vivo

Morsli

Henriques

Ellis

et al. 2022

Preprint

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“…The transparency of zebrafish embryos and the optically clear adult casper lines have escalated the diverse potential of this model in generating transgenic zebrafish lines that express fluorescent tissue-specific proteins or express mammalian oncogenes under a zebrafish tissue-specific promoter [ 49 , 71 , 83 , 126 , 127 ]. These models not only facilitate the in vivo monitoring of basic developmental processes, such as cell division, migration and differentiation, but allows the in vivo real-time tracking of cancer development and pathogenesis, aiding in the search for novel therapeutics [ 93 , 128 , 129 , 130 , 131 , 132 ].…”

Section: Zebrafish Models Of Paediatric Brain Cancermentioning

confidence: 99%

Zebrafish Models of Paediatric Brain Tumours

Basheer

Dhar

Samarasinghe

2022

IJMS

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Paediatric brain cancer is the second most common childhood cancer and is the leading cause of cancer-related deaths in children. Despite significant advancements in the treatment modalities and improvements in the 5-year survival rate, it leaves long-term therapy-associated side effects in paediatric patients. Addressing these impairments demands further understanding of the molecularity and heterogeneity of these brain tumours, which can be demonstrated using different animal models of paediatric brain cancer. Here we review the use of zebrafish as potential in vivo models for paediatric brain tumour modelling, as well as catalogue the currently available zebrafish models used to study paediatric brain cancer pathophysiology, and discuss key findings, the unique attributes that these models add, current challenges and therapeutic significance.

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“…Animal models, such as mouse, chicken, frog and zebrafish, provide an important avenue to gain better mechanistic and genetic insights into human craniofacial development [5]. Zebrafish offer many advantages as a model system that make them ideal for detailed craniofacial studies — they develop externally and generate large numbers of transparent embryos, which permits unparalleled high-resolution imaging of specific cell types and structures in living vertebrates [7,8,9,10,11,12]. Zebrafish craniofacial development, particularly craniofacial bone and cartilage formation, has been well characterized and is comparable to aminote craniofacial development.…”

Section: Introductionmentioning

confidence: 99%

zFACE: Facial Analytics from a Coordinate Extrapolation System for Developing Zebrafish

Maili

Ruíz

Kahan

et al. 2022

Preprint

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Facial development requires a complex and coordinated series of cellular events, that when perturbed, can lead to structural birth defects. A standardized quantitative approach to quickly assess morphological changes could address how genetic or environmental inputs lead to differences in facial development. Here we report on a method to rapidly analyze craniofacial development in zebrafish embryos that combines a simple staining and mounting paradigm with Facial Analytics based on a Coordinate Extrapolation system, termed zFACE. Confocal imaging of frontal/rostral mounted embryos generates high-resolution images to capture facial structures and morphometric data is quantified based on a coordinate system that assesses 26 anatomical landmarks present at defined times in development. The semi-automated analysis can be applied to embryos at different stages of development and quantitative morphometric data can detect subtle phenotypic variation. Shape analysis can also be performed with the coordinate data to inform on global changes in facial morphology. We applied this new approach to show that loss of smarca4a in developing zebrafish leads to craniofacial anomalies, microcephaly and alterations in brain morphology. These changes are characteristic of humans with Coffin-Siris syndrome (CSS), a rare genetic disorder associated with mutations in SMARCA4 that is defined by anomalies in head size, intellectual disabilities and craniofacial abnormalities. We observed that smarca4a is expressed in craniofacial tissues and our multivariate analysis facilitated the classification of smarca4a mutants based on changes in specific phenotypic characteristics. Together, our approach provides a way to rapidly and quantitatively assess the impact of genetic alterations on craniofacial development in zebrafish.

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Transgenic fluorescent zebrafish lines that have revolutionized biomedical research

Cited by 45 publications

References 368 publications

A p21-GFP zebrafish model of senescence for rapid testing of senolyticsin vivo

A p21-GFP zebrafish model of senescence for rapid testing of senolyticsin vivo

Zebrafish Models of Paediatric Brain Tumours

zFACE: Facial Analytics from a Coordinate Extrapolation System for Developing Zebrafish

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