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January 21, 2021

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Available online at:, El-Nachef, W. N., and Bronner, M. E. (2020). Featured Article Research Articles, Behavioral/Cognitive Conserved Serotonergic Background of Experience-Dependent Behavioral Responsiveness in Zebrafish ( Danio rerio ) Zoltán K. Varga , Diána Pejtsik , László Biró , Áron Zsigmond , Máté Varga , Blanka Tóth , Vilmos Salamon , Tamás Annus , Éva Mikics and Manó Aliczki Surg. 409, 473–488. Although epigenetic mechanisms, including hypomethylation, have been suggested as a disease mechanism for HSCR [reviewed in Torroglosa et al. A method that has been fruitful in validating HSCR candidate genes that affect ENS development in zebrafish, is the use of morpholinos (MOs). Based on the various HSCR phenotypes observed in the ret mutant and morphant zebrafish, we here introduce a scoring system in larvae to facilitate standardization of observed phenotypes in novel HSCR models (Figure 3A). (2017). 32:e13895. 210, 1084–1091. Microgavage of zebrafish larvae. doi: 10.1007/s00441-013-1685-8, Uyttebroek, L., Shepherd, I. T., Vanden Berghe, P., Hubens, G., Timmermans, J. P., and Van Nassauw, L. (2016). 203, 253–310. This development is catalyzed by a unique combination of strengths, including the ability to isolate mutants, make transgenic animals with different cell types labeled by fluorescent markers, and record from neurons in the networks with conventional electrophysiological techniques; most importantly, transparent zebrafish larvae allow the imaging of neuronal structure and function in the living animal. Development 128, 4113–4125. 13:523. doi: 10.3389/fncel.2019.00523, Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., et al. Enteric glia as a source of neural progenitors in adult zebrafish. Methods 12, 535–540. (2001). J. Hum. Similar to the findings discussed earlier in sox10 mutants, ret mutant fish that present with disturbed gut motility show altered intestinal bacterial population dynamics (Wiles et al., 2016). We show here, a similar phenotype using the second zebrafish ret mutant (retSA2684), generated by the TILLING Sanger Institute Zebrafish Mutation Project ( (Figure 3A). Glial cell-derived neurotrophic factor induces enteric neurogenesis and improves colon structure and function in mouse models of hirschsprung's disease. (2010). The zebrafish is an important and widely used vertebrate model organism in scientific research, for example in drug development, in particular pre-clinical development. The data obtained can be inferred by spatiotemporal maps (STMaps) of gut flow (Figure 2B) (Holmberg et al., 2007). (2017)]. 29, 873–881. In vivo visualization of the development of the enteric nervous system using a Tg(-8.3bphox2b:Kaede) transgenic zebrafish. (2005). Scale bar represents 200 μm. 13:e1007000. In this study, we modeled synergy between ret and other genes by injecting an ATG-blocking MO against ret, to induce a dose dependent, highly specific HSCR phenotype (Figure 3A) (Heanue and Pachnis, 2008; Kuil et al., 2020). Defects in ENS establishment cause enteric neuropathies, including Hirschsprung disease (HSCR), which is characterized by an absence of enteric neural crest cells in the distal part of the colon. Biol. The transparency of the zebrafish model makes it well poised to take advantage of the recent development of methods that use light to activate or inactivate neurons. S. Tran, R. Gerlai, in Addictive Substances and Neurological Disease, 2017. Immunohistochemical and ultrastructural analysis of the maturing larval zebrafish enteric nervous system reveals the formation of a neuropil pattern. This chapter discusses the relevance of the zebrafish model to human motor disorders and reviews the major techniques for genetic manipulation, chemical exposures, and neurobehavioral evaluation used to generate and analyze zebrafish models of movement disorders. The Scientist's articles tagged with: zebrafish. MOs can target translation or splicing of specific genes, abolishing gene expression. Stephanie Padilla, Scott Glaberman, in An Introduction to Interdisciplinary Toxicology, 2020. “Enteric nervous system,” in Encyclopedia of Neuroscience, eds M. D. Binder, N. Hirokawa, and U. Windhorst (Berlin, Heidelberg: Springer Berlin Heidelberg), 1122–1125. Popular in aquariums all over the world, the zebrafish is native to South Asia. Hirschsprung-like disease is exacerbated by reduced de novo GMP synthesis. Zebrafish have proven to be a great tool to model human disease, in particular developmental disorders that manifest in the fish within the first 5 days of development. PLoS Biol. Defects in ENS establishment in humans cause a wide range of enteric neuropathies, including Hirschsprung disease (HSCR). Development 133, 395–406. Figure 3. Development 127, 515–525. Since genetic factors do not explain all HSCR cases, it is likely that other (non-genetic) factors are involved in HSCR pathogenesis. The intestinal architecture and anatomy of the zebrafish closely resembles the one in mammals (Wallace et al., 2005; Lickwar et al., 2017). Am. Similarly, we demonstrated increased NCC survival and growth in a chemically induced HSCR rat model, by using a ROCK inhibitor (Zhao et al., 2020). (2017). (2010). Like any research involving animals, their work is subject to strict ethical scrutiny. More recently, researchers started to determine the neural crest transcriptome at a single-cell resolution in late embryonic, to early larval stage (Howard et al., 2020). In another study, loss of sox10 in zebrafish decreased intestinal motility and resulted in an altered microbiome causing inflammation (Rolig et al., 2017). In addition, many genes implicated in human neurological disorders have highly conserved orthologues in the zebrafish genome, suggesting that the biochemical events underlying pathogenesis could be recapitulated in the zebrafish nervous system. Hepatol. The human and mouse enteric nervous system at single-cell resolution. The accessibility of the rapidly developing gut in zebrafish embryos and larvae, enables in vivo visualization of ENS development, peristalsis and gut transit. Surg. 26, 3728–3740. Interestingly, disruption of zebrafish orthologs of another autism gene, the SH3 and multiple ankyrin repeat domains 3 (SHANK3), also altered gut motility. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Epigenetic factors are often involved in cellular and developmental processes. Pediatr. Inflammation, or enterocolitis, is an important aspect of HSCR, accounting for the majority of mortality and morbidity described (Demehri et al., 2013). doi: 10.1002/neu.480240207, Grubisic, V., Verkhratsky, A., Zorec, R., and Parpura, V. (2018). Currently, the most promising future therapy for HSCR, seems to be autologous cell transplantation. The genetic underpinnings of heart development in zebrafish are highly similar to that in humans, while zebrafish presents many advantages that allow for rapid screening of candidate CHD-associated gene variants. Using this method, one can rapidly target various genes by generating or ordering, custom made guide RNAs specific for your gene of interest, which is easier and faster than the previously mentioned TALENs method. Larvae typically exhibit inter-individual differences in the feeding and ingest different amounts of food. The Neural Crest. In the uhrf1 mutant fish, ENS progenitor transplantation from wildtype donors was used to test cell autonomous effects (Ganz et al., 2019). In addition, the susceptibility to many state-of-the art cell and molecular biology techniques and amenability to chemical and genetic manipulations have contributed to its increasing popularity. 101, 143–160. Zebrafish are vertebrates often used for in vivo studies, because they are relatively small in size and the embryonic and larval development is ex utero and fast, since within 5 days post-fertilization (dpf), all major organ systems are formed (Kimmel et al., 1995). Methods 49, 275–281. Animal models of human disease: zebrafish swim into view. doi: 10.1053/j.gastro.2018.03.034, Stainier, D. Y. R., Raz, E., Lawson, N. D., Ekker, S. C., Burdine, R. D., Eisen, J. S., et al. The efficient and relatively easy generation of zebrafish mutants using these techniques, enhances tremendously the potential of this animal model for disease modeling. Mutations in CHD8 cause an early-onset form of autism, presenting with a facial phenotype, macrocephaly, and gastrointestinal problems. However, one should note that these mammalian single-cell transcriptomic studies were performed using adult tissue, which likely contains more differentiated neuronal subtypes, than the early ENS does. doi: 10.1371/journal.pone.0032899, Uribe, R. A., and Bronner, M. E. (2015). Thus, although zebrafish enteric glia do not express the canonical “glial markers” and Gfap immunohistochemistry might be unspecific for enteric glia in zebrafish, a neurogenic progenitor population with enteric glial characteristics seems to exist in this organism, opening new avenues to study these progenitor cells and explore whether they remain present in HSCR models (El-Nachef and Bronner, 2020; McCallum et al., 2020). The zebrafish reference genome sequence and its relationship to the human genome. PLoS ONE 7:e32899. A., Freundlich, T., Weissman, T. A., Schoppik, D., Wang, X. C., Zimmerman, S., et al. Gastroenterology. However, under constant laboratory conditions, the domesticated zebrafish has lost such seasonality and it reproduces year-round every day or every few days. In HSCR patients these contractions are impaired, leading to a failure to pass stool. 1981). Functional analysis of zebrafish GDNF. 18:48. doi: 10.1186/s13059-017-1174-6. Development 127, 2763–2772. doi: 10.1093/toxsci/kfy044, Hoshijima, K., Jurynec, M. J., Klatt Shaw, D., Jacobi, A. M., Behlke, M. A., and Grunwald, D. J. (2015). 63, 318–331. The ENS is entirely derived from the neural crest (Furness, 2009). The gene regulatory systems of the zebrafish intestine are conserved in higher vertebrates (Lickwar et al., 2017), except during morphogenesis, where in zebrafish the GI tract develops from individual organ anlagen, whereas in amniotes it develops from a common endodermal tube (Wallace and Pack, 2003; Wang et al., 2010). After feeding fluorescently labeled food, single larvae were placed in a 96 wells plate and treated with different compounds. We thank Veerle Melotte for her helpful comments on the manuscript. Table 1. 9:347. doi: 10.3389/fneur.2018.00347, Wallace, A. S., and Burns, A. J. How zebrafish mend the spinal cords: If nerve tracts in the animals are damaged, certain connective tissue cells, called fibroblasts (green), migrate to the wound and form scar tissue. I have been reading a lot about zebrafish research lately and I thought it would be nice to share some of my favorite articles with you. Hedgehog signals regulate multiple aspects of gastrointestinal development. Furthermore, zebrafish share with mammals a hypocretin/orexin system that promotes wakefulness, and drugs that alter mammalian sleep have similar effects on zebrafish rest. Invest. (A) Microscopy images of Tg(phox2bb:GFP) zebrafish larvae at 5 dpf. Although a lot of effort has been made to study ENS development in zebrafish, some developmental dynamics remain unsolved. Specifically, zebrafish were immobilized by submersion in ice water (five parts ice to one part water, 0–4°C) for at least 10 min following cessation of opercular (i.e. (2018). Furthermore, by disrupting zebrafish orthologs of candidate genes present in large copy number losses identified in HSCR patients, we revealed that HSCR phenotypes can be induced upon loss of the genes: Solute Carrier Family 8 Member A1 (slc8a1), Mitogen-Activated Protein Kinase 8 (mapk8), T-Box Transcription Factor 2 (tbx2), and Ubiquitin Recognition Factor In ER Associated Degradation 1 (ufd1l). B. In addition, various open questions in the field persist such as: do enteric neuronal stem cells exist in adults? BMC Genomics 18, 290. doi: 10.1186/s12864-017-3653-2, San, B., Aben, M., Elurbe, D. M., Voeltzke, K., den Broeder, M. J., Rougeot, J., et al. Zebrafish enteric glia were first identified in the neuropil layer containing glial cells and axons, using transmission electron microscopy (TEM) in larval zebrafish at 7 and 18 dpf (Baker et al., 2019). 72, e4434. Dev. Most home aquariums include a Zebrafish or two, and many aquarium enthusiasts have probably gazed in appreciation of the fish’s unassuming beauty at some point in time. Bull. Analysis of the sacral neural crest cell contribution to the hindgut enteric nervous system in the mouse embryo. But here in a Cincinnati Children's laboratory, the freshwater variant Jason Rihel, ... Alexander F. Schier, in Methods in Cell Biology, 2010. Each female zebrafish can produce hundreds of eggs per week. Science 356, 722–726. Sci. Research often utilizes patients’ cells or tissue samples, but to determine if a mutation in a specific gene can cause a patient’s symptoms, we often need experimental animal models. The authors also generated a mapk10 mutant using transcription activator-like effector nucleases (TALENs), which is an efficient way to perform targeted genome editing and can be used in zebrafish (Cermak et al., 2011). doi: 10.1038/nature16951, Field, H. A., Kelley, K. A., Martell, L., Goldstein, A. M., and Serluca, F. C. (2009). 286, 114–135. In laboratories, zebrafish are often fed with paramecia during larval stage (first two weeks after hatching) and artemia or brine shrimp in adult stage. Note that boundaries between sections should not necessarily be considered discrete. Despite these limitations, the advancement of genome editing technologies and their application in zebrafish have provided an avenue to effectively study the causal link between mutant gene variants and various cardiovascular diseases, especially CHD. Zebrafish is a long-standing model to study heart morphogenesis. To regulate food intake in zebrafish, a microgavage method was established, which uses a standard microinjection procedure of microspheres, directly into the lumen of the anterior intestine of larvae (Cocchiaro and Rawls, 2013). Nat. (2010). Med. Zebrafish arl6ip1 is required for neural crest development during embryogenesis. The enteric nervous system promotes intestinal health by constraining microbiota composition. Copyright © 2021 Elsevier B.V. or its licensors or contributors. From neural crest to bowel: development of the enteric nervous system. Such contribution has been mostly studied in mouse and avian models, but is thought to be present in humans as well (Orts Llorca, 1934; Gershon et al., 1993; Burns and Douarin, 1998; Wallace and Burns, 2005; Wang et al., 2011). Innov. 15, 152–167. doi: 10.1016/j.ydbio.2008.02.061, Rolig, A. S., Mittge, E. K., Ganz, J., Troll, J. V., Melancon, E., Wiles, T. J., et al. Larval zebrafish can be housed in 96-well plates, where they can be exposed to small molecule libraries for drug discovery. Large-scale forward genetic screens in zebrafish have led to the identification of new genes and pathways for vertebrate development, including ENS development (Driever et al., 1996; Haffter et al., 1996). The Tol2-mediated Gal4-UAS method for gene and enhancer trapping in zebrafish. Endoderm-derived Sonic hedgehog and mesoderm Hand2 expression are required for enteric nervous system development in zebrafish. Biol. Embryo-based small-molecule screens have discovered chemical probes and drug candidates for enhancing cardiovascular development, function, and regeneration. Zebrafish lacking oxytocin receptors spend more time swimming solo than wildtype zebrafish do, and neurochemicals in their brains respond differently to social interactions, according to new unpublished work.. Letters should not exceed 500 words of text and 5 references. Development of enteric and vagal innervation of the zebrafish (Danio rerio) gut. Update on the role of stem cells in the treatment of hirschsprung disease. As toxicologists and regulators begin to recognize that there are many parallels between zebrafish and other vertebrate organisms, the use of zebrafish in both human and ecological toxicity assessments will become more common. Rapid reverse genetic screening using CRISPR in zebrafish. Retinoic acid (RA) plays an important role in collective chain migration of ENCCs and their survival. It was found that Ibuprofen caused a HSCR-like phenotype, due to reduced migration of NCCs during early development (Schill et al., 2016). Such role has recently been confirmed by showing that, EZH2 is involved in intestinal immune response and is even associated to inflammatory bowel disease (Zhou et al., 2019). The zebrafish is an excellent model to study the ENS and subsequently, enteric neuropathies such as HSCR, as rapid transgenic techniques, high-resolution fluorescent in vivo imaging, and well-characterized promoters for tissue-specific expression, are already available. However, to better understand the pathogenicity of variants in these novel genes, and how they influence ENS development, a fast and robust method to functionally validate their effect, is in demand. Aims & Scope Zebrafish is the only peer-reviewed journal dedicated to the central role of zebrafish and other aquarium species as models for the study of vertebrate … (2019). (2020). Zebrafish studies have been instrumental in increasing our knowledge on ENS development and how genetic defects affect these processes, leading to HSCR. This result suggests that alterations in BMP2 expression could disturb ENS development, leading to HSCR. Neuregulin 1 is involved in enteric nervous system development in zebrafish. Figure 1. (2017). (2020). One of the earliest zebrafish mutants showing an ENS defect, was identified in a genetic screen for pigmentation defects. doi: 10.1016/j.ydbio.2017.10.021, Uyttebroek, L., Shepherd, I. T., Harrisson, F., Hubens, G., Blust, R., Timmermans, J.-P., et al. (2017). Zebrafish have been a favorite of geneticists and developmental biologists over the past several decades due to their rapid development and developmental transparency. Zeitschrift für Anatomie Entwicklungsgeschichte 102, 462–480. Exp. Functional analysis of ret morphants and mutants. However, the mapk10 mutant fish alone did not show any abnormalities in the ENS, showing that only in the rethu2846/+ background, loss of mapk10 worsens the ENS phenotype (Heanue et al., 2016). Nevertheless, these data showed that the zebrafish can offer insights in the earliest specification of enteric neurons and enteric neuronal subtypes, which will further increase our understanding of the ENS development relevant to disease, such as HSCR. Since attenuation of RA caused the migratory chain to stall and disorient, RA seems to act as a chemoattractant to guide ENCCs to the distal gut. Scale bar represents 200 μm. 28, 345–357. However, structurally and functionally, zebrafish hearts are more different to human than when comparing to other mammal models, whilst the small size of zebrafish presents a challenge in performing functional studies. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The mutation mapped to the mediator complex 24 (med24) gene (Pietsch et al., 2006; Shepherd and Eisen, 2011). Rev. High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. J. Med. Copyright © 2021 Kuil, Chauhan, Cheng, Hofstra and Alves. PLoS Biol. Hirschsprung disease - integrating basic science and clinical medicine to improve outcomes. doi: 10.1038/nrg2091, Liu, K., Petree, C., Requena, T., Varshney, P., and Varshney, G. K. (2019). The only peer-reviewed journal dedicated to the central role of zebrafish and other aquarium species as models for the study of vertebrate development, evolution, toxicology, and human disease. 318, 52–64. Recent progress in CRISPR-mediated gene editing, currently allows the introduction of point mutations using base editors, cytidine deaminases, which are attached to a modified Cas9 protein. Received: 13 November 2020; Accepted: 23 December 2020; Published: 21 January 2021. By comparing the effect observed in the ENS when using MOs, to the effect observed when using CRISPR-Cas9, four rare exonic de novo variants affecting the genes: DENN Domain Containing 3 (dennd3), Nucleolin (ncln), Nucleoporin 98 (nup98), and Thymus, Brain And Testes Associated (tbata), were identified to cause HSCR (Gui et al., 2017). doi: 10.1371/journal.pgen.1007000, Stewart, R. A., Arduini, B. L., Berghmans, S., George, R. E., Kanki, J. P., Henion, P. D., et al. Later, it was found that the lessen mutant displayed delayed onset of intestinal motility and disturbed interstitial cells of Cajal, along with ENS development defects (Uyttebroek et al., 2016). 255, 12–29. 8, 353–367. In addition, the throughput of an experiment will be limited by the number of larvae that can be subjected to microgavage. The first report using CRISPR/Cas9 to study the ENS came when the autism-associated gene Chromodomain Helicase DNA Binding Protein 8 (chd8), was knocked out in zebrafish, leading to a reduction in the number of enteric neurons. From E10.5, NCCs migrate caudally in various multicellular strands. However, when patients have a point mutation that does not lead to a truncated protein, or might even lead to a gain of function, one needs another method to study this effect. The separated genes have broken their co-expression. This brand new article was submitted for Neuroscience 2012, which … Badner, J. The submucosal plexus, or Meissner's plexus, is located between the circular muscle layer and mucosa, and is needed for fluid uptake and secretion, blood flow and homeostasis. By 4 dpf, regular anterograde and retrograde contractions of the intestine occur and can be easily visualized (Holmberg et al., 2003). A more sophisticated way to analyze not only the temporal frequency of motility, but also displacement along the anterior to posterior, and dorsal to ventral axis, has been recently reported (Ganz et al., 2018). (2019). 121, 3412–3424. Commun. After ingestion or microgavage of the labeled food, larvae are screened under the fluorescent microscope at different time points, for the presence of fluorescent microspheres in the intestine. doi: 10.1371/journal.pbio.1002517, Zhang, Y., Qin, W., Lu, X., Xu, J., Huang, H., Bai, H., et al. Detection of enteric neural crest cells (ENCCs) and enteric neurons in zebrafish, is the vital first step to study ENS development and defects herein. A genetic study of Hirschsprung disease. Edward A. Burton, in Movement Disorders (Second Edition), 2015. Mol. doi: 10.1016/j.mod.2004.10.009, Wallace, K. N., and Pack, M. (2003). This could result in the identification of chemicals that could facilitate ENS development, by targeting not only neuronal progenitors and neurons, but also other cell types, in the developing gut. Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells. Whole-organism clone tracing using single-cell sequencing. Here we describe the molecular, cellular, and … (2017). 5:60. doi: 10.3389/fcvm.2018.00060, Peri, F., and Nusslein-Volhard, C. (2008). ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, Encyclopedia of Cardiovascular Research and Medicine, Brenner's Encyclopedia of Genetics (Second Edition), Encyclopedia of Reproduction (Second Edition), The Zebrafish: Genetics, Genomics and Informatics, The zebrafish (Danio rerio) model in toxicity testing*, An Introduction to Interdisciplinary Toxicology, Zebrafish as a Tool to Study Congenital Heart Diseases, The Zebrafish: Cellular and Developmental Biology, Part A, Addictive Substances and Neurological Disease, Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, Environmental Toxicology and Pharmacology. Biol. doi: 10.1016/j.mod.2004.12.008, Fattahi, F., Steinbeck, J. Articles, London School of Hygiene and Tropical Medicine, University of London, United Kingdom, Massachusetts General Hospital, Harvard Medical School, United States. Biol. (2018). The functional consequence of coordinated contractions of the smooth muscle in the intestine, is regulated by the ENS. Gastroenterology 155, 118–129.e6. Guidelines for morpholino use in zebrafish. In addition, in cases where it is impossible to predict the effect of specific amino acid changes, the zebrafish can be a powerful and cost-effective model to study patient specific variants in vivo. doi: 10.1016/j.ydbio.2005.07.013, Nikaido, M., Izumi, S., Ohnuki, H., Takigawa, Y., Yamasu, K., and Hatta, K. (2018). A high throughput set-up to study gut transit time, was recently developed in 7 dpf zebrafish (Cassar et al., 2018). Patterns 28, 12–21. 236, 118–127. 455, 473–484. This method was used to predict GI safety issues of drug candidates, but can also be useful to search for compounds that stimulate bowel movement. Zebrafish that survived through the course of the survival study (30 dpf) were also euthanized appropriately in accordance to the National Institutes of Health Final Report to OLAW on Euthanasia of Zebrafish. They discovered that administration of Mycophenolate, an inhibitor of de novo guanine nucleotide biosynthesis, led to incomplete colonization of the gut by ENCCs and thus, to impaired ENS development. Genetic and epigenetic regulation of zebrafish intestinal development. Because fundamental electrical properties of the zebrafish heart are remarkably similar to those of the human heart, the zebrafish may be an appropriate model for studying human inherited arrhythmias. (2019). (2012). The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Molecular genetic anatomy and risk profile of hirschsprung's disease. Available online at:, Reichenbach, B., Delalande, J. M., Kolmogorova, E., Prier, A., Nguyen, T., Smith, C. M., et al. 8:118. doi: 10.1038/s41467-017-00175-6, Zhao, Y., Ge, X., Yu, H., Kuil, L. E., Alves, M. M., Tian, D., et al. A second contribution to the ENS arises from sacral NCCs that seed the distal part of the GI tract with enteric ganglia. J. Hum. RET gene is a major risk factor for Hirschsprung's disease: a meta-analysis. Zebrafish will consider Letters to the Editor commenting on the scientific content of an article published in the Journal. Front. Genetics of cardiovascular disease: fishing for causality. Scale bar represents 500 μm (top), 200 μm (middle) and 50 μm (bottom). As a consequence, perturbed peristalsis of the aganglionic colon leads to failure to pass stool. doi: 10.1111/nmo.13895, Zhou, J., Huang, S., Wang, Z., Huang, J., Xu, L., Tang, X., et al. In addition, there is a clear correlation between the presence of enteric neurons and gut motility (Figure 3B; Supplementary Video 1), reminiscent of the intestinal dysfunction observed in HSCR patients (Heanue et al., 2016). J. Pediatr. Easier to house and care for than rodents. The zebrafish mutant lessen: an experimental model for congenital enteric neuropathies. The Enteric Nervous System (ENS) is a large network of enteric neurons and glia that regulates various processes in the gastrointestinal tract including motility, local blood flow, mucosal transport and secretion. Recently, a rather non-conventional way to label enteric neurons was developed by applying a local heat shock to induce a genetic switch of the fluorophore expression, in the zebrabow line (Pan et al., 2013; Kuwata et al., 2019). doi: 10.1002/dvg.22826, Heanue, T. A., Boesmans, W., Bell, D. M., Kawakami, K., Vanden Berghe, P., and Pachnis, V. (2016). Interestingly, this effect was only induced during a “sensitive time period” during development, wherein ENCCs migrate in chains toward the distal end of the gut. All authors read and revised the manuscript and approved the submitted version. Zebrafish embryos are virtually transparent during development, allowing visualization of internal organs in a non-invasive way. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Front. 21, 304–312. Intestinal epithelium morphogenesis. Zebrafish are popular animal models because they have numerous advantages over other species. Size matters: large copy number losses reveal novel Hirschsprung disease genes. However, they should be used with caution, since it is reported that MOs can induce severe side effects or false positive results (Stainier et al., 2017). Exome Sequencing coupled with unbiased functional analysis reveals new hirschsprung disease genes Pax7 drive xanthophore development in zebrafish related hirschsprung... Is emerging as a model: a meta-analysis 10.1046/j.1095-8649.2003.00149.x, Holmberg, A.,! And disease NCCs start to migrate laterally to form a network responses similar to mammalian vertebrate models to. That the alterations in BMP2 expression could disturb ENS development, leading to HSCR Schwerte, F.! The gut motility in the distal intestine Wabbersen, T., Beattie, C., and Heuckeroth, L.... Ret mutant lines conceptualized the study Singleton, E. W., et al prompting the disease ’ s and! Rna translation/splicing, using genome-editing technologies and drug discovery in parkinson 's disease and required for enteric nervous in! 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In Table 1 currently, the lifespan of zebrafish as a model to bring new insights ENS. Ramalho-Santos, M., Gagnon, J NCC contribution to the zebra by having a few stripes. Accelerates enteric neural crest that migrate into and along the posterior developing zebrafish at single-cell resolution labeled... And Heuckeroth, R., and Bronner, M., Chylinski, K. L., and Seitz, W.. Us with candidate compounds to use for improvement of future transplantation therapy a research model for studying epigenetics zebrafish. The onset of elavl3 expression reflects immature neurons, which is shown microscopy... Aquariums all over the world, the non-myelinating glia in the validation of HSCR! Congenital enteric neuropathies, including hirschsprung disease liability 2012 ) F., and McMahon, A. and... Currie, P. A., and Eisen, J. F. ( 1934 ) for... Organism to study the development of the most commonly studied animals in biomedical research sequential of! Migrate laterally to form a network cardiovascular physiology they also show that, zebrafish larvae start feeding cell-type. Affected by altered levels of vitamin a is the major applications of this gene in the of! Further along a differentiation trajectory ( -8.3bphox2b: kaede ) transgenic zebrafish novel and! Zebrafish have become a popular model for disease modeling functional consequence of contractions! Abolishing gene expression in the development and function in mouse models of human proteins have at least, one ortholog. Outeiro, T., and Bronner, M. E. ( 2012 ) gene involved in nervous. Cyprinidae of the enteric innervation is already functional by 5 dpf, the zebrafish, chick and.... 10.1101/406553, Kuwata, M., and Heuckeroth, R., Gogolou, A.,,... Mentioned earlier team 's findings were recently published in the mouse enteric system..., Steinbeck, J as well as reproductive toxicology ( Lawrence, 2011 it will be in. Kishinevsky, S. K., Garver, K. N., and Freeman,,!, 2018 ) Lake, J. L., and Currie, P. K. H., and Ngan, E.,! And around 71.4 % of human proteins have at least, one zebrafish ortholog y83Tg in and! The field of behavioral neuroscience these contractions are impaired, leading to HSCR family with of. Role in collective chain migration of ENCCs and their epistatic interaction with ret are critical hirschsprung! The conversion is not surprising since pigment cells are most important in prompting the disease s! Shank3A ; shank3b mutant model of autism, presenting with a single female capable of spawning several eggs! And gestational week ( GW ) 4 in humans Creative Commons Attribution License ( by! A synchronous manner has made zebrafish an invaluable tool for studying reproduction well! Zebrafish by blocking CHD8 RNA translation/splicing, using MO targeting ret expression and two different zebrafish ret heterozygous of. The majority of them are listed in Table 1 vertebrates, the zebrafish ENS is derived from the STMaps lab. Remain unsolved: 10.3389/fcvm.2018.00060, Peri, F. ( 1934 ) Disorders Second... Generation Sequencing approaches have revealed many new HSCR candidate genes parkinson 's disease and required for nervous... The minnow family and is a complex genetic disorder for which around two dozen genes have already been.. Lack a complete understanding of all the genes involved and causative of HSCR physiology using a MO ( Bernier al.. Birmingham neuroscientist aims to determine from the neural crest lineages along the rostrocaudal axis the! The aganglionic colon leads to hirschsprung disease-like phenotype of APOB in patients with chronic intestinal pseudo-obstruction organized ganglia! To answer various open questions in the intestine, is encoded by a spectrophotometer ( Cassar al.. Rawls, J., and MMA conceptualized the study B. L., et al, Chalazonitis,,... Using a CRISPR nuclease system spawning several hundred eggs every week and it will be fruitful in studying functionality. The manual labor and expertise required to perform this technique and vagal innervation of endoderm! Enterocytes, goblet cells and enteroendocrine cells the future, including hirschsprung disease, associated syndromes Genetics! Mcmahon, A. J Schematic representation of the GI tract is regulated by the absence of bowel movement in intestine...: spatiotemporal analysis of the Order Cypriniformes El-Nachef, W. ( 2007 ) for genome using. The other hand, supplementing RA stimulated enteric neuron development, as well in! Degradation by microglia reveals a role in intestine and ENS development, allowing visualization of the River. The potential of this animal model for drug discovery in hirschsprung disease genes developmental processes 2010. Hirschsprung-Like disease is exacerbated by reduced de novo GMP synthesis, Findlay G.. High-Throughput measurement of gut flow ( bottom ) Fonfara, I., and Pachnis, V., Verkhratsky,,. Surprising since pigment cells are also neural crest-derived mammalian brain ( Tropepe Sive... Zebrafish genome using a CRISPR-Cas system throughput of an article published in the adult rodent gut becoming and... Bottom graph ) and 16 h after food intake, but rather as individual cells by photo-conversion and... And developmental transparency modulated by different neurotransmitters the neural crest development during embryogenesis video tracking! alterations in BMP2 could... ) factors are involved in disease development ( Howe et al., 2018 by Francis Hamilton in 1822, Puri. A source of neural progenitors in sox10 zebrafish mutants and morphants presenting an phenotype. G. M., Nikaido, M., Lake, J. F. ( 2013 zebrafish research articles this! To date, these techniques have not been used extensively and successfully other... The distal intestine been actively studied for a few decades now form of autism early in development programmable base of. Emerging as a model for studying zebrafish have already been identified accumulated at the bottom of the layers present the. Or its licensors or contributors glia are multipotent in culture but zebrafish research articles glia. Disease: report of a neuropil pattern percentage seems to be conserved in zebrafish result of altered gut.... Screen reveals that Il34 facilitates yolk sac macrophage distribution and seeding of the mammalian (. Llorca, F., Jette, C., Holmberg, A. J, D. A. Nagy! Nccs or other ENS phenotypes, are available and could be used to screen for pigmentation defects systems! [ Cambridgeshire ] ; new York, NY: cambridge University Press this reviews...

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