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Biomedicines
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Zebrafish Models for Development and Disease 2.0
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Zebrafish Models for Development and Disease 2.0

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

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 39514

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

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
Dr. Swapnalee Sarmah

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

Special Issue Information

Dear Colleagues,

This Special Issue is the second volume of our previous Special Issue “Zebrafish Models for Development and Disease”. The zebrafish has become an important model organism to study normal development, particularly since large-scale genetic screening was used to identify genes that control developmental mechanisms. Subsequently, a large variety of creative approaches were used to develop disease models that are used to study developmental disorders, cancer, heart disease, diabetes, and many other conditions. The advent of next-generation DNA sequencing techniques expanded the utility of the zebrafish model, allowing analysis of genetic and epigenetic mechanisms of development and disease. Additionally, the small size, imaging capabilities, and reporter gene expression in the zebrafish permits high throughput toxicology evaluation and drug screening, increasing the capability of this model. The zebrafish is increasingly being used to study neurological, psychiatric, and behavioral conditions. This call for papers invites contributions of original research and reviews for this Special Issue of Biomedicines entitled “Zebrafish Models in Development and Disease”. The Special Issue will explore the diverse capabilities of the zebrafish model that can be applied to study a growing list of biological and preclinical research problems.

Scope:

  • Basic research using the zebrafish model to understand diseases and mechanisms;
  • Basic research using the zebrafish to model disease treatment strategies;
  • Basic research using the zebrafish to evaluate potential teratogens;
  • Basic research using the zebrafish for drug screening;
  • Basic research using the zebrafish for neuroscience and behavioral studies;
  • Review articles on describing any of the above topics using the zebrafish model organism.

Prof. James A. Marrs
Dr. Swapnalee Swapnalee Sarmah
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • disease model
  • drug screening model
  • teratogen screening
  • toxicological screening
  • neuroscience
  • behavior
  • developmental biology

Related Special Issues

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

4 pages, 156 KiB  
Editorial
The Genius of the Zebrafish Model: Insights on Development and Disease
by James A. Marrs and Swapnalee Sarmah
Biomedicines 2021, 9(5), 577; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050577 - 20 May 2021
Cited by 3 | Viewed by 2149
Abstract
The zebrafish is an outstanding and inexpensive vertebrate model system for biomedical research [...] Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)

Research

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13 pages, 6896 KiB  
Article
Functional Role of the RNA-Binding Protein Rbm24a and Its Target sox2 in Microphthalmia
by Lindy K. Brastrom, C. Anthony Scott, Kai Wang and Diane C. Slusarski
Biomedicines 2021, 9(2), 100; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9020100 - 21 Jan 2021
Cited by 4 | Viewed by 2123
Abstract
Congenital eye defects represent a large class of disorders affecting roughly 21 million children worldwide. Microphthalmia and anophthalmia are relatively common congenital defects, with approximately 20% of human cases caused by mutations in SOX2. Recently, we identified the RNA-binding motif protein 24a (Rbm24a) [...] Read more.
Congenital eye defects represent a large class of disorders affecting roughly 21 million children worldwide. Microphthalmia and anophthalmia are relatively common congenital defects, with approximately 20% of human cases caused by mutations in SOX2. Recently, we identified the RNA-binding motif protein 24a (Rbm24a) which binds to and regulates sox2 in zebrafish and mice. Here we show that morpholino knockdown of rbm24a leads to microphthalmia and visual impairment. By utilizing sequential injections, we demonstrate that addition of exogenous sox2 RNA to rbm24a-deplete embryos is sufficient to suppress morphological and visual defects. This research demonstrates a critical role for understanding the post-transcriptional regulation of genes needed for development. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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Graphical abstract

20 pages, 4190 KiB  
Article
Method Standardization for Conducting Innate Color Preference Studies in Different Zebrafish Strains
by Petrus Siregar, Stevhen Juniardi, Gilbert Audira, Yu-Heng Lai, Jong-Chin Huang, Kelvin H.-C. Chen, Jung-Ren Chen and Chung-Der Hsiao
Biomedicines 2020, 8(8), 271; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8080271 - 03 Aug 2020
Cited by 20 | Viewed by 4352
Abstract
The zebrafish has a tetrachromatic vision that is able to distinguish ultraviolet (UV) and visible wavelengths. Recently, zebrafish color preferences have gained much attention because of the easy setup of the instrument and its usefulness to screen behavior-linked stimuli. However, several published papers [...] Read more.
The zebrafish has a tetrachromatic vision that is able to distinguish ultraviolet (UV) and visible wavelengths. Recently, zebrafish color preferences have gained much attention because of the easy setup of the instrument and its usefulness to screen behavior-linked stimuli. However, several published papers dealing with zebrafish color preferences have contradicting results that underscore the importance of method standardization in this field. Different laboratories may report different results because of variations in light source, color intensity, and other parameters such as age, gender, container size, and strain of fish. In this study, we aim to standardize the color preference test in zebrafish by measuring light source position, light intensity, gender, age, animal size to space ratio, and animal strain. Our results showed that color preferences for zebrafish are affected by light position, age, strain, and social interaction of the fish, but not affected by fish gender. We validated that ethanol can significantly induce color preference alteration in zebrafish which may be related to anxiety and depression. We also explored the potential use of the optimized method to examine color preference ranking and index differences in various zebrafish strains and species, such as the tiger barb and glass catfish. In conclusion, zebrafish color preference screening is a powerful tool for high-throughput neuropharmacological applications and the standardized protocol established in this study provides a useful reference for the zebrafish research community. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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31 pages, 24183 KiB  
Article
Orthosiphon stamineus Proteins Alleviate Pentylenetetrazol-Induced Seizures in Zebrafish
by Yin-Sir Chung, Brandon Kar Meng Choo, Pervaiz Khalid Ahmed, Iekhsan Othman and Mohd. Farooq Shaikh
Biomedicines 2020, 8(7), 191; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8070191 - 02 Jul 2020
Cited by 11 | Viewed by 2850
Abstract
The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure [...] Read more.
The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800 µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the “Synaptic Vesicle Cycle” pathway. OSLP’s anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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15 pages, 2435 KiB  
Article
Early Exposure to THC Alters M-Cell Development in Zebrafish Embryos
by Md Ruhul Amin, Kazi T. Ahmed and Declan W. Ali
Biomedicines 2020, 8(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8010005 - 04 Jan 2020
Cited by 13 | Viewed by 4711
Abstract
Cannabis is one of the most commonly used illicit recreational drugs that is often taken for medicinal purposes. The psychoactive ingredient in cannabis is Δ9-Tetrahydrocannabinol (Δ9-THC, hereafter referred to as THC), which is an agonist at the endocannabinoid receptors [...] Read more.
Cannabis is one of the most commonly used illicit recreational drugs that is often taken for medicinal purposes. The psychoactive ingredient in cannabis is Δ9-Tetrahydrocannabinol (Δ9-THC, hereafter referred to as THC), which is an agonist at the endocannabinoid receptors CB1R and CB2R. Here, we exposed zebrafish embryos to THC during the gastrulation phase to determine the long-term effects during development. We specifically focused on reticulospinal neurons known as the Mauthner cells (M-cell) that are involved in escape response movements. The M- cells are born during gastrulation, thus allowing us to examine neuronal morphology of neurons born during the time of exposure. After the exposure, embryos were allowed to develop normally and were examined at two days post-fertilization for M-cell morphology and escape responses. THC treated embryos exhibited subtle alterations in M-cell axon diameter and small changes in escape response dynamics to touch. Because escape responses were altered, we also examined muscle fiber development. The fluorescent labelling of red and white muscle fibers showed that while muscles were largely intact, the fibers were slightly disorganized with subtle but significant changes in the pattern of expression of nicotinic acetylcholine receptors. However, there were no overt changes in the expression of nicotinic receptor subunit mRNA ascertained by qPCR. Embryos were allowed to further develop until 5 dpf, when they were examined for overall levels of movement. Animals exposed to THC during gastrulation exhibited reduced activity compared with vehicle controls. Together, these findings indicate that zebrafish exposed to THC during the gastrula phase exhibit small changes in neuronal and muscle morphology that may impact behavior and locomotion. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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15 pages, 5232 KiB  
Article
Intracellular Localization in Zebrafish Muscle and Conserved Sequence Features Suggest Roles for Gelatinase A Moonlighting in Sarcomere Maintenance
by Amina M. Fallata, Rachael A. Wyatt, Julie M. Levesque, Antoine Dufour, Christopher M. Overall and Bryan D. Crawford
Biomedicines 2019, 7(4), 93; https://doi.org/10.3390/biomedicines7040093 - 29 Nov 2019
Cited by 15 | Viewed by 3136
Abstract
Gelatinase A (Mmp2 in zebrafish) is a well-characterized effector of extracellular matrix remodeling, extracellular signaling, and along with other matrix metalloproteinases (MMPs) and extracellular proteases, it plays important roles in the establishment and maintenance of tissue architecture. Gelatinase A is also found moonlighting [...] Read more.
Gelatinase A (Mmp2 in zebrafish) is a well-characterized effector of extracellular matrix remodeling, extracellular signaling, and along with other matrix metalloproteinases (MMPs) and extracellular proteases, it plays important roles in the establishment and maintenance of tissue architecture. Gelatinase A is also found moonlighting inside mammalian striated muscle cells, where it has been implicated in the pathology of ischemia-reperfusion injury. Gelatinase A has no known physiological function in muscle cells, and its localization within mammalian cells appears to be due to inefficient recognition of its N-terminal secretory signal. Here we show that Mmp2 is abundant within the skeletal muscle cells of zebrafish, where it localizes to the M-line of sarcomeres and degrades muscle myosin. The N-terminal secretory signal of zebrafish Mmp2 is also challenging to identify, and this is a conserved characteristic of gelatinase A orthologues, suggesting a selective pressure acting to prevent the efficient secretion of this protease. Furthermore, there are several strongly conserved phosphorylation sites within the catalytic domain of gelatinase A orthologues, some of which are phosphorylated in vivo, and which are known to regulate the activity of this protease. We conclude that gelatinase A likely participates in uncharacterized physiological functions within the striated muscle, possibly in the maintenance of sarcomere proteostasis, that are likely regulated by kinases and phosphatases present in the sarcomere. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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Review

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18 pages, 1167 KiB  
Review
Zebra-Fishing for Regenerative Awakening in Mammals
by Laura Massoz, Marie Alice Dupont and Isabelle Manfroid
Biomedicines 2021, 9(1), 65; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9010065 - 12 Jan 2021
Cited by 6 | Viewed by 3744
Abstract
Regeneration is defined as the ability to regrow an organ or a tissue destroyed by degeneration or injury. Many human degenerative diseases and pathologies, currently incurable, could be cured if functional tissues or cells could be restored. Unfortunately, humans and more generally mammals [...] Read more.
Regeneration is defined as the ability to regrow an organ or a tissue destroyed by degeneration or injury. Many human degenerative diseases and pathologies, currently incurable, could be cured if functional tissues or cells could be restored. Unfortunately, humans and more generally mammals have limited regenerative capabilities, capacities that are even further declining with age, contrary to simpler organisms. Initially thought to be lost during evolution, several studies have revealed that regenerative mechanisms are still present in mammals but are latent and thus they could be stimulated. To do so there is a pressing need to identify the fundamental mechanisms of regeneration in species able to efficiently regenerate. Thanks to its ability to regenerate most of its organs and tissues, the zebrafish has become a powerful model organism in regenerative biology and has recently engendered a number of studies attesting the validity of awakening the regenerative potential in mammals. In this review we highlight studies, particularly in the liver, pancreas, retina, heart, brain and spinal cord, which have identified conserved regenerative molecular events that proved to be beneficial to restore murine and even human cells and which helped clarify the real clinical translation potential of zebrafish research to mammals. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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23 pages, 1176 KiB  
Review
An Overview of Methods for Cardiac Rhythm Detection in Zebrafish
by Fiorency Santoso, Ali Farhan, Agnes L. Castillo, Nemi Malhotra, Ferry Saputra, Kevin Adi Kurnia, Kelvin H.-C. Chen, Jong-Chin Huang, Jung-Ren Chen and Chung-Der Hsiao
Biomedicines 2020, 8(9), 329; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8090329 - 04 Sep 2020
Cited by 18 | Viewed by 6417
Abstract
The heart is the most important muscular organ of the cardiovascular system, which pumps blood and circulates, supplying oxygen and nutrients to peripheral tissues. Zebrafish have been widely explored in cardiotoxicity research. For example, the zebrafish embryo has been used as a human [...] Read more.
The heart is the most important muscular organ of the cardiovascular system, which pumps blood and circulates, supplying oxygen and nutrients to peripheral tissues. Zebrafish have been widely explored in cardiotoxicity research. For example, the zebrafish embryo has been used as a human heart model due to its body transparency, surviving several days without circulation, and facilitating mutant identification to recapitulate human diseases. On the other hand, adult zebrafish can exhibit the amazing regenerative heart muscle capacity, while adult mammalian hearts lack this potential. This review paper offers a brief description of the major methodologies used to detect zebrafish cardiac rhythm at both embryonic and adult stages. The dynamic pixel change method was mostly performed for the embryonic stage. Other techniques, such as kymography, laser confocal microscopy, artificial intelligence, and electrocardiography (ECG) have also been applied to study heartbeat in zebrafish embryos. Nevertheless, ECG is widely used for heartbeat detection in adult zebrafish since ECG waveforms’ similarity between zebrafish and humans is prominent. High-frequency ultrasound imaging (echocardiography) and modern electronic sensor tag also have been proposed. Despite the fact that each method has its benefits and limitations, it is proved that zebrafish have become a promising animal model for human cardiovascular disease, drug pharmaceutical, and toxicological research. Using those tools, we conclude that zebrafish behaviors as an excellent small animal model to perform real-time monitoring for the developmental heart process with transparent body appearance, to conduct the in vivo cardiovascular performance and gene function assays, as well as to perform high-throughput/high content drug screening. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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18 pages, 727 KiB  
Review
Marijuana and Opioid Use during Pregnancy: Using Zebrafish to Gain Understanding of Congenital Anomalies Caused by Drug Exposure during Development
by Swapnalee Sarmah, Marilia Ribeiro Sales Cadena, Pabyton Gonçalves Cadena and James A. Marrs
Biomedicines 2020, 8(8), 279; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8080279 - 08 Aug 2020
Cited by 8 | Viewed by 4240
Abstract
Marijuana and opioid addictions have increased alarmingly in recent decades, especially in the United States, posing threats to society. When the drug user is a pregnant mother, there is a serious risk to the developing baby. Congenital anomalies are associated with prenatal exposure [...] Read more.
Marijuana and opioid addictions have increased alarmingly in recent decades, especially in the United States, posing threats to society. When the drug user is a pregnant mother, there is a serious risk to the developing baby. Congenital anomalies are associated with prenatal exposure to marijuana and opioids. Here, we summarize the current data on the prevalence of marijuana and opioid use among the people of the United States, particularly pregnant mothers. We also summarize the current zebrafish studies used to model and understand the effects of these drug exposures during development and to understand the behavioral changes after exposure. Zebrafish experiments recapitulate the drug effects seen in human addicts and the birth defects seen in human babies prenatally exposed to marijuana and opioids. Zebrafish show great potential as an easy and inexpensive model for screening compounds for their ability to mitigate the drug effects, which could lead to new therapeutics. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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13 pages, 541 KiB  
Review
Studying the Pathophysiology of Parkinson’s Disease Using Zebrafish
by Lisa M. Barnhill, Hiromi Murata and Jeff M. Bronstein
Biomedicines 2020, 8(7), 197; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8070197 - 07 Jul 2020
Cited by 23 | Viewed by 4907
Abstract
Parkinson’s disease is a common neurodegenerative disorder leading to severe disability. The clinical features reflect progressive neuronal loss, especially involving the dopaminergic system. The causes of Parkinson’s disease are slowly being uncovered and include both genetic and environmental insults. Zebrafish have been a [...] Read more.
Parkinson’s disease is a common neurodegenerative disorder leading to severe disability. The clinical features reflect progressive neuronal loss, especially involving the dopaminergic system. The causes of Parkinson’s disease are slowly being uncovered and include both genetic and environmental insults. Zebrafish have been a valuable tool in modeling various aspects of human disease. Here, we review studies utilizing zebrafish to investigate both genetic and toxin causes of Parkinson’s disease. They have provided important insights into disease mechanisms and will be of great value in the search for disease-modifying therapies. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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