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Biomedicines
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Zebrafish Models for Development and Disease 4.0
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Zebrafish Models for Development and Disease 4.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 25323

Special Issue Editor

Prof. Dr. James A. Marrs

E-Mail Website
Guest Editor
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA
Interests: zebrafish; fetal alcohol spectrum disorder; gastrulation; congenital heart defects; eye defects; cadherin; tight junction; adherens junction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The zebrafish is an important model organism that is used to study normal development, genetic diseases and influences of environmental toxins. Advanced, cutting-edge technologies such as gene editing, next-generation DNA sequencing and transgenic techniques have produced experimental approaches in the zebrafish model that address mechanisms of development and vertebrate evolution. Increasingly, the zebrafish is being used to explore the neural structures that control behavior, which have applications in neurology, psychology and psychiatry. The zebrafish has advantages for neurobiology because its brain is simpler than that of mammals, but the structures, neurochemistry and behaviors have a high degree of conservation relative to other vertebrates. This call for papers invites contributions of original research and reviews for this Special Issue of Biomedicines entitled “Zebrafish Models in Development and Disease”. This Special Issue will explore the diverse capabilities of the zebrafish model that can be applied to biological and preclinical research.

Prof. Dr. James A. Marrs
Guest Editor

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Published Papers (10 papers)

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Research

Jump to: Review

20 pages, 2316 KiB  
Article
The Impact of Polychlorinated Biphenyls on the Development of Zebrafish (Danio rerio)
by Megan Moma, Abi Lee, M. Brady Olson, Karin L. Lemkau and W. James Cooper
Biomedicines 2024, 12(9), 2068; https://doi.org/10.3390/biomedicines12092068 - 10 Sep 2024
Viewed by 806
Abstract
Polychlorinated biphenyls (PCBs) are a group of 209 highly stable molecules that were used extensively in industry. Although their commercial use ceased in 1979, they are still present in many aquatic ecosystems due to improper disposal, oceanic currents, atmospheric deposition, and hydrophobic nature. [...] Read more.
Polychlorinated biphenyls (PCBs) are a group of 209 highly stable molecules that were used extensively in industry. Although their commercial use ceased in 1979, they are still present in many aquatic ecosystems due to improper disposal, oceanic currents, atmospheric deposition, and hydrophobic nature. PCBs pose a significant and ongoing threat to the development and sustainability of aquatic organisms. In areas with PCB exposure high mortality rates of organisms inhabiting them are still seen today, posing a significant threat to local species. Zebrafish were exposed to a standard PCB mixture (Aroclor 1254) for the first 5 days post fertilization, as there is a gap in knowledge during this important developmental period for fish (i.e., organization of the body). This PCB mixture was formally available commercially and has a high prevalence in PCB-contaminated sites. We tested for the effects of PCB dosage (control (embryo water only; 0 mg/L), methanol (solvent control; 0 mg/L); PCB 1 (0.125 mg/L), PCB 2 (0.25 mg/L), PCB 3 (0.35 mg/L), and PCB 4 (0.40 mg/L)) on zebrafish survival, rate of metamorphosis, feeding efficiency, and growth. We found significant, dose-dependent effects of PCB exposure on mortality, feeding efficiency, and growth, but no clear effect of PCBs on the rate of zebrafish metamorphosis. We identified a concentration in which there were no observable effects (NOEC), PCB concentration above the NOEC had a significant impact on life-critical processes. This can further inform local management decisions in environments experiencing PCB contamination. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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17 pages, 5500 KiB  
Article
Behavioral Effects of the Mixture and the Single Compounds Carbendazim, Fipronil, and Sulfentrazone on Zebrafish (Danio rerio) Larvae
by Samara da Silva Gomes, Jadson Freitas da Silva, Renata Meireles Oliveira Padilha, João Victor Alves de Vasconcelos, Luís Gomes de Negreiros Neto, James A. Marrs and Pabyton Gonçalves Cadena
Biomedicines 2024, 12(6), 1176; https://doi.org/10.3390/biomedicines12061176 - 25 May 2024
Viewed by 912
Abstract
Pesticides are often detected in freshwater, but their impact on the aquatic environment is commonly studied based on single compounds, underestimating the potential additive effects of these mixtures. Even at low concentrations, pesticides can negatively affect organisms, altering important behaviors that can have [...] Read more.
Pesticides are often detected in freshwater, but their impact on the aquatic environment is commonly studied based on single compounds, underestimating the potential additive effects of these mixtures. Even at low concentrations, pesticides can negatively affect organisms, altering important behaviors that can have repercussions at the population level. This study used a multi-behavioral approach to evaluate the effects of zebrafish larvae exposure to carbendazim (C), fipronil (F), and sulfentrazone (S), individually and mixed. Five behavioral tests, thigmotaxis, touch sensitivity, optomotor response, bouncing ball test, and larval exploratory behavior, were performed to assess potential effects on anxiety, fear, and spatial and social interaction. Significant changes were observed in the performance of larvae exposed to all compounds and their mixtures. Among the single pesticides, exposure to S produced the most behavioral alterations, followed by F and C, respectively. A synergistic effect between the compounds was observed in the C + F group, which showed more behavioral effects than the groups exposed to pesticides individually. The use of behavioral tests to evaluate pesticide mixtures is important to standardize methods and associate behavioral changes with ecologically relevant events, thus creating a more realistic scenario for investigating the potential environmental impacts of these compounds. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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13 pages, 2257 KiB  
Article
Essential Oils Produce Developmental Toxicity in Zebrafish Embryos and Cause Behavior Changes in Zebrafish Larvae
by Ivanildo Inacio da Silva, Jr., Niely Priscila Correia da Silva, James A. Marrs and Pabyton Gonçalves Cadena
Biomedicines 2023, 11(10), 2821; https://doi.org/10.3390/biomedicines11102821 - 18 Oct 2023
Viewed by 2387
Abstract
Essential oils have gained significant popularity in various industries due to their biological properties, but their potential toxic effects on living organisms have been poorly investigated. This study aimed to evaluate the effects of lemongrass, thyme, and oregano essential oils on zebrafish embryos [...] Read more.
Essential oils have gained significant popularity in various industries due to their biological properties, but their potential toxic effects on living organisms have been poorly investigated. This study aimed to evaluate the effects of lemongrass, thyme, and oregano essential oils on zebrafish embryos and larvae as animal models. Embryos were exposed to different concentrations of essential oils, and various endpoints were assessed, including epiboly, mortality (LC50), morphometry, and behavioral changes. All three essential oils reduced epiboly, affecting embryonic development. LC50 values were calculated for lemongrass (3.7 µg/mL), thyme (14.4 µg/mL), and oregano (5.3 µg/mL) oils. Larvae exposed to these oils displayed morphological defects, including growth reduction, spinal deformation, pericardial edema, eye size reduction, and reduced swim-bladder inflation. Morphometric analysis confirmed reduced larval length at higher oil concentrations. Essential-oil exposure altered zebrafish larval swimming behavior, with lemongrass oil reducing dark-cycle activity and oregano oil increasing light-cycle activity, suggesting neurodevelopmental toxicity. These findings illustrate the adverse effects of these oils on zebrafish embryos and larvae and reveal essential-oil toxicity, indicating careful use should be considered, particularly during pregnancy. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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14 pages, 3090 KiB  
Article
Development of a Transparent Transgenic Zebrafish Cellular Phenotype Tg(6xNF-kB:EGFP); Casper(roy−/−, nacre−/−) to Study NF-kB Activity
by Surendra K. Rajpurohit, Logan Ouellette, Suvarsha Sura, Chelsea Appiah, Annabelle O’Keefe, Katherine McCarthy, Umasai Kandepu, May Ye Mon, Kirk Kimmerling, Vishal Arora and Bal L. Lokeshwar
Biomedicines 2023, 11(7), 1985; https://doi.org/10.3390/biomedicines11071985 - 13 Jul 2023
Viewed by 5955
Abstract
NF-κB signaling has broad effects on cell survival, tissue growth, and proliferation activities. It controls many genes that are involved in inflammation and thus is a key player in many inflammatory diseases. The elevation of NF-κB activators is associated with elevated mortality, especially [...] Read more.
NF-κB signaling has broad effects on cell survival, tissue growth, and proliferation activities. It controls many genes that are involved in inflammation and thus is a key player in many inflammatory diseases. The elevation of NF-κB activators is associated with elevated mortality, especially in cancer and cardiovascular diseases. The zebrafish has emerged as an important model for whole-organism in vivo modeling in translational research. In vertebrates, in-vivo spatial resolution is limited due to normal opacification of skin and subdermal structure. For in vivo imaging, skin transparency by blocking the pigmentation via chemical inhibition is required and the maintenance of this transparency is vital. The Casper(roy−/−, nacre−/−) mutant of zebrafish maintains this transparency throughout its life and serves as an ideal combination of sensitivity and resolution for in vivo stem cell analyses and imaging. We developed an NF-kB:GFP/Casper transparent transgenic zebrafish cellular phenotype to study inflammatory processes in vivo. We outline the experimental setup to generate a transparent transgenic NF-kB/Casper strain of zebrafish through the cross-breeding of Casper and NF-kB transgenic adult fish and have generated F01 in the form of heterozygous progeny. The transgenic F01 progeny was further inbred to generate heterozygous progenies from F1 to F4 generations. Furthermore, it continued to successfully develop the homozygous strain Tg(6xNF-kB:EGFP); Casper(roy−/−, nacre−/−) in the F05 generation. This novel strain of F05 generation showed 100% homozygosity in the transgenic transparent progeny of Tg(6xNF-kB:EGFP); Casper(roy−/−, nacre−/−). The strain has been confirmed by generating the F06 generation of homozygous progeny and again verified and validated for its homogeneity in the F07 generation. The newly developed novel transparent transgenic strain of the NF-kB reporter line has been coined as “Tg(6xNF-kB:EGFP); Casper(roy−/−, nacre−/−)gmc1”. We have established a newly generated phenotype of transparent transgenic zebrafish for time-lapse in vivo confocal microscopy to study the cellular phenotype and pathologies at the cellular level over time. This will allow for quantifying the changes in the NF-kB functional activities over time and allow the comparison of control and cardiac-oncology experimental therapeutics. We validated the newly developed Tg(6xNF-kB:EGFP); Casper(roy−/−, nacre−/−)gmc1 homozygous strain of zebrafish by studying the inflammatory response to bacterial lipopolysaccharide (LPS) exposure, tolerance, and the inhibitory role of a potential novel drug candidate against LPS-induced inflammation. The results establish the unique application of newly developed strains by identifying hit and lead drug candidates for experimental therapeutics. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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17 pages, 3748 KiB  
Article
Super-Resolution Imaging Reveals the Nanoscale Distributions of Dystroglycan and Integrin Itga7 in Zebrafish Muscle Fibers
by Komala Shivanna, Mary Astumian, Prakash Raut, Vinh-Nhan Ngo, Samuel T. Hess and Clarissa Henry
Biomedicines 2023, 11(7), 1941; https://doi.org/10.3390/biomedicines11071941 - 8 Jul 2023
Viewed by 1669
Abstract
Cell signaling is determined partially by the localization and abundance of proteins. Dystroglycan and integrin are both transmembrane receptors that connect the cytoskeleton inside muscle cells to the extracellular matrix outside muscle cells, maintaining proper adhesion and function of muscle. The position and [...] Read more.
Cell signaling is determined partially by the localization and abundance of proteins. Dystroglycan and integrin are both transmembrane receptors that connect the cytoskeleton inside muscle cells to the extracellular matrix outside muscle cells, maintaining proper adhesion and function of muscle. The position and abundance of Dystroglycan relative to integrins is thought to be important for muscle adhesion and function. The subcellular localization and quantification of these receptor proteins can be determined at the nanometer scale by FPALM super-resolution microscopy. We used FPALM to determine localizations of Dystroglycan and integrin proteins in muscle fibers of intact zebrafish (Danio rerio). Results were consistent with confocal imaging data, but illuminate further details at the nanoscale and show the feasibility of using FPALM to quantify interactions of two proteins in a whole organism. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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21 pages, 6329 KiB  
Article
Surface Electrical Impedance Myography Detects Skeletal Muscle Atrophy in Aged Wildtype Zebrafish and Aged gpr27 Knockout Zebrafish
by Seward B. Rutkove, Zsu-Zsu Chen, Sarbesh Pandeya, Santiago Callegari, Tyler Mourey, Janice A. Nagy and Anjali K. Nath
Biomedicines 2023, 11(7), 1938; https://doi.org/10.3390/biomedicines11071938 - 7 Jul 2023
Cited by 3 | Viewed by 1947
Abstract
Throughout a vertebrate organism’s lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia is associated with risk of falling, cardiovascular disease, and all-cause mortality. As the world population ages, projected to reach 2 billion older [...] Read more.
Throughout a vertebrate organism’s lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia is associated with risk of falling, cardiovascular disease, and all-cause mortality. As the world population ages, projected to reach 2 billion older adults worldwide in 2050, the economic burden on the healthcare system is also projected to increase considerably. Currently, there are no pharmacological treatments for sarcopenia, and given the long-term nature of aging studies, high-throughput chemical screens are impractical in mammalian models. Zebrafish is a promising, up-and-coming vertebrate model in the field of sarcopenia that could fill this gap. Here, we developed a surface electrical impedance myography (sEIM) platform to assess skeletal muscle health, quantitatively and noninvasively, in adult zebrafish (young, aged, and genetic mutant animals). In aged zebrafish (~85% lifespan) as compared to young zebrafish (~20% lifespan), sEIM parameters (2 kHz phase angle, 2 kHz reactance, and 2 kHz resistance) robustly detected muscle atrophy (p < 0.000001, q = 0.000002; p = 0.000004, q = 0.000006; p = 0.000867, q = 0.000683, respectively). Moreover, these same measurements exhibited strong correlations with an established morphometric parameter of muscle atrophy (myofiber cross-sectional area), as determined by histological-based morphometric analysis (r = 0.831, p = 2 × 10−12; r = 0.6959, p = 2 × 10−8; and r = 0.7220; p = 4 × 10−9, respectively). Finally, the genetic deletion of gpr27, an orphan G-protein coupled receptor (GPCR), exacerbated the atrophy of skeletal muscle in aged animals, as evidenced by both sEIM and histology. In conclusion, the data here show that surface EIM techniques can effectively discriminate between healthy young and sarcopenic aged muscle as well as the advanced atrophied muscle in the gpr27 KO animals. Moreover, these studies show how EIM values correlate with cell size across the animals, making it potentially possible to utilize sEIM as a “virtual biopsy” in zebrafish to noninvasively assess myofiber atrophy, a valuable measure for muscle and gerontology research. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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21 pages, 6682 KiB  
Article
gldc Is Essential for Renal Progenitor Patterning during Kidney Development
by Nicole E. Weaver, Allison Healy and Rebecca A. Wingert
Biomedicines 2022, 10(12), 3220; https://doi.org/10.3390/biomedicines10123220 - 12 Dec 2022
Cited by 9 | Viewed by 2523
Abstract
The glycine cleavage system (GCS) is a complex located on the mitochondrial membrane that is responsible for regulating glycine levels and contributing one-carbon units to folate metabolism. Congenital mutations in GCS components, such as glycine decarboxylase (gldc), cause an elevation in [...] Read more.
The glycine cleavage system (GCS) is a complex located on the mitochondrial membrane that is responsible for regulating glycine levels and contributing one-carbon units to folate metabolism. Congenital mutations in GCS components, such as glycine decarboxylase (gldc), cause an elevation in glycine levels and the rare disease, nonketotic hyperglycinemia (NKH). NKH patients suffer from pleiotropic symptoms including seizures, lethargy, mental retardation, and early death. Therefore, it is imperative to fully elucidate the pathological effects of gldc dysfunction and glycine accumulation during development. Here, we describe a zebrafish model of gldc deficiency that recapitulates phenotypes seen in humans and mice. gldc deficient embryos displayed impaired fluid homeostasis suggesting renal abnormalities, as well as aberrant craniofacial morphology and neural development defects. Whole mount in situ hybridization (WISH) revealed that gldc transcripts were highly expressed in the embryonic kidney, as seen in mouse and human repository data, and that formation of several nephron segments was disrupted in gldc deficient embryos, including proximal and distal tubule populations. These kidney defects were caused by alterations in renal progenitor populations, revealing that the proper function of Gldc is essential for the patterning of this organ. Additionally, further analysis of the urogenital tract revealed altered collecting duct and cloaca morphology in gldc deficient embryos. Finally, to gain insight into the molecular mechanisms underlying these disruptions, we examined the effects of exogenous glycine treatment and observed analogous renal and cloacal defects. Taken together, these studies indicate for the first time that gldc function serves an essential role in regulating renal progenitor development by modulating glycine levels. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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Review

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16 pages, 715 KiB  
Review
Zebrafish as a Model for Multiple Sclerosis
by Briana Maktabi, Abigail Collins, Raihaanah Safee, Jada Bouyer, Alexander S. Wisner, Frederick E. Williams and Isaac T. Schiefer
Biomedicines 2024, 12(10), 2354; https://doi.org/10.3390/biomedicines12102354 - 16 Oct 2024
Viewed by 1096
Abstract
Background: Zebrafish have become a key model organism in neuroscience research because of their unique advantages. Their genetic, anatomical, and physiological similarities to humans, coupled with their rapid development and transparent embryos, make them an excellent tool for investigating various aspects of neurobiology. [...] Read more.
Background: Zebrafish have become a key model organism in neuroscience research because of their unique advantages. Their genetic, anatomical, and physiological similarities to humans, coupled with their rapid development and transparent embryos, make them an excellent tool for investigating various aspects of neurobiology. They have specifically emerged as a valuable and versatile model organism in biomedical research, including the study of neurological disorders such as multiple sclerosis. Multiple sclerosis is a chronic autoimmune disease known to cause damage to the myelin sheath that protects the nerves in the brain and spinal cord. Objective: This review emphasizes the importance of continued research in both in vitro and in vivo models to advance our understanding of MS and develop effective treatments, ultimately improving the quality of life for those affected by this debilitating disease. Conclusions: Recent studies show the significance of zebrafish as a model organism for investigating demyelination and remyelination processes, providing new insights into MS pathology and potential therapies. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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32 pages, 978 KiB  
Review
Embryonic Zebrafish as a Model for Investigating the Interaction between Environmental Pollutants and Neurodegenerative Disorders
by Ji-Hang Yin and Katharine A. Horzmann
Biomedicines 2024, 12(7), 1559; https://doi.org/10.3390/biomedicines12071559 - 13 Jul 2024
Cited by 1 | Viewed by 967
Abstract
Environmental pollutants have been linked to neurotoxicity and are proposed to contribute to neurodegenerative disorders. The zebrafish model provides a high-throughput platform for large-scale chemical screening and toxicity assessment and is widely accepted as an important animal model for the investigation of neurodegenerative [...] Read more.
Environmental pollutants have been linked to neurotoxicity and are proposed to contribute to neurodegenerative disorders. The zebrafish model provides a high-throughput platform for large-scale chemical screening and toxicity assessment and is widely accepted as an important animal model for the investigation of neurodegenerative disorders. Although recent studies explore the roles of environmental pollutants in neurodegenerative disorders in zebrafish models, current knowledge of the mechanisms of environmentally induced neurodegenerative disorders is relatively complex and overlapping. This review primarily discusses utilizing embryonic zebrafish as the model to investigate environmental pollutants-related neurodegenerative disease. We also review current applicable approaches and important biomarkers to unravel the underlying mechanism of environmentally related neurodegenerative disorders. We found embryonic zebrafish to be a powerful tool that provides a platform for evaluating neurotoxicity triggered by environmentally relevant concentrations of neurotoxic compounds. Additionally, using variable approaches to assess neurotoxicity in the embryonic zebrafish allows researchers to have insights into the complex interaction between environmental pollutants and neurodegenerative disorders and, ultimately, an understanding of the underlying mechanisms related to environmental toxicants. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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21 pages, 1801 KiB  
Review
Zebrafish as a Model to Study Retinoic Acid Signaling in Development and Disease
by Matthew R. Hawkins and Rebecca A. Wingert
Biomedicines 2023, 11(4), 1180; https://doi.org/10.3390/biomedicines11041180 - 15 Apr 2023
Cited by 6 | Viewed by 5515
Abstract
Retinoic acid (RA) is a metabolite of vitamin A (retinol) that plays various roles in development to influence differentiation, patterning, and organogenesis. RA also serves as a crucial homeostatic regulator in adult tissues. The role of RA and its associated pathways are well [...] Read more.
Retinoic acid (RA) is a metabolite of vitamin A (retinol) that plays various roles in development to influence differentiation, patterning, and organogenesis. RA also serves as a crucial homeostatic regulator in adult tissues. The role of RA and its associated pathways are well conserved from zebrafish to humans in both development and disease. This makes the zebrafish a natural model for further interrogation into the functions of RA and RA-associated maladies for the sake of basic research, as well as human health. In this review, we explore both foundational and recent studies using zebrafish as a translational model for investigating RA from the molecular to the organismal scale. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 4.0)
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