Inflammation, or enterocolitis, is an important aspect of HSCR, accounting for the majority of mortality and morbidity described (Demehri et al., 2013). (2011). Interestingly, transplanted wildtype cells were absent from the distal-most region in the mutants, showing that Uhrf1 function is necessary in non-neuronal cells in the intestine, for ENS progenitors to migrate to the far end of the intestine (Ganz et al., 2019). The utility of zebrafish (Danio rerio) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Specifically, neural crest cells (NCCs) migrate from the hindbrain, the vagal region of the neural tube, into and along the entire length of the GI tract (Le Douarin, 1982). For example, with respect to ENS lineages and differentiation paths of enteric glia, enteric progenitors and enteric neurons. An independent study, also reported the presence of neurogenic precursors in adult zebrafish, that lack expression of the canonical “glial marker” Gfap (El-Nachef and Bronner, 2020). J. Mol. Each female zebrafish can produce hundreds of eggs per week. As mentioned in the previous section, retinoic acid increases enteric neuron numbers in vivo and is currently also used in vitro to enhance specification of enteric neural progenitors (Frith et al., 2020). J. Pediatr. doi: 10.1016/j.brainresbull.2017.03.011, Gui, H., Schriemer, D., Cheng, W. W., Chauhan, R. K., Antinolo, G., Berrios, C., et al. Dev. J. Hum. Epigenetic factors are often involved in cellular and developmental processes. Scale bar represents 200 μm. Please let me know what your favorite zebrafish article is by commenting below! Therefore, measuring gut motility can be used to assess the consequences of alterations in ENS development, such as the ones leading to HSCR. Zebrafish have proven to be a great tool to model human disease, in particular developmental disorders that manifest … 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wildtype zebrafish do, and neurochemicals in their brains respond differently to social interactions, according to new unpublished work.. Interestingly, Bmp2 was found to directly regulate expression of the glial-derived neurotrophic factor (Gdnf), a known HSCR gene and ligand of Ret. doi: 10.1055/s-0038-1646925, Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., et al. doi: 10.1038/nature12111, Huang, S., Wang, Y., Luo, L., Li, X., Jin, X., Li, S., et al. Nature 531, 105–109. Zebrafish have been a favorite of geneticists and developmental biologists over the past several decades due to their rapid development and developmental transparency. Nature 556, 108–112. World J. Gastroenterol. doi: 10.1016/S0012-1606(02)00034-9, Wang, X., Chan, A. K., Sham, M. H., Burns, A. J., and Chan, W. Y. Biotechnol. Dev. Simultaneous lineage tracing and cell-type identification using CRISPR-Cas9-induced genetic scars. 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. The efficient and relatively easy generation of zebrafish mutants using these techniques, enhances tremendously the potential of this animal model for disease modeling. Therefore, a pre-sorting is warranted to reduce variability. Dev. 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). eLife 2:e00471. Thereby, several parameters such as, wave duration, wave speed and amplitude, were able to be measured (Ganz et al., 2018). 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. Front. Intestinal growth and differentiation in zebrafish. (2005). In the next sections, we discuss some of the approaches currently used to genetically modify or block, expression of specific ENS genes using zebrafish, in an attempt to provide insights into the genetics and mechanisms underlying HSCR development. (2015). doi: 10.1016/j.ydbio.2015.09.023, Shah, A. N., Davey, C. F., Whitebirch, A. C., Miller, A. C., and Moens, C. B. Proposed phenotyping classifications are shown by microscopy images and illustrations. However, the conversion is not permanent, limiting extended live-imaging experiments. However, mutant zebrafish lines that exhibit HSCR or other ENS phenotypes, are available and could be used for this purpose. doi: 10.1172/JCI58200, Lasrado, R., Boesmans, W., Kleinjung, J., Pin, C., Bell, D., Bhaw, L., et al. Analysis of gastrointestinal physiology using a novel intestinal transit assay in zebrafish. MO injections in zebrafish also showed that blocking ihh, reduced the number of enteric neurons present in the intestine, confirming its previously described role in ENS development shown in mice, and its reminiscence to HSCR (Ramalho-Santos et al., 2000; Sribudiani et al., 2018). Dev Cell 51, 645–657 e4. Although a lot of effort has been made to study ENS development in zebrafish, some developmental dynamics remain unsolved. Dis. While zebrafish was originally considered as a bridge connection in the experimental gap between fly/worm and mouse/human in studying embryo development, it was shown that as the new research methodologies and genetic tools were updated, the zebrafish animal model was reported to be well suited to both developmental and genetic analysis as well as complex human disorders [19, 20]. The zebrafish is a powerful vertebrate model used to dissect molecular pathways of cardiovascular development and disease. 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. 121, 3398–3411. The results obtained showed expression in the zebrafish ENS of known markers of the mammalian ENS, but also revealed previously unidentified genes that are enriched in the ENS. Sequential actions of Pax3 and Pax7 drive xanthophore development in zebrafish neural crest. (C) Microscopic images of Tg(phox2bb:GFP) zebrafish larvae fed with fluorescently labeled food, showing typical intestinal transit and describing the transitional zone. High-throughput measurement of gut transit time using larval zebrafish. doi: 10.1016/j.mod.2008.04.006, Heuckeroth, R. O. Expanding the CRISPR toolbox in zebrafish for studying development and disease. *Correspondence: Laura E. Kuil, l.kuil@erasmusmc.nl, †These authors have contributed equally to this work, Front. The current pathophysiological model is that failure of NCCs to migrate, differentiate, proliferate or survive, thereby forming a functional ENS network, results in HSCR. Dev. |, The Mammalian ENS and Its Role in Human Disease, Zebrafish As a Model Organism for Developmental Disorders, Zebrafish as a Model Organism to Study the ENS, Genetic Modifications in Zebrafish to Study ENS Development, Role of Non-genetic Factors on ENS Development Leading to HSCR, Identification of Drugs That Stimulate ENS Development, https://doi.org/10.3389/fcell.2020.629073, https://www.sanger.ac.uk/resources/zebrafish/, https://www.frontiersin.org/articles/10.3389/fcell.2020.629073/full#supplementary-material, https://dev.biologists.org/content/128/21/4113.long, https://dev.biologists.org/content/127/3/515, https://dev.biologists.org/content/127/12/2763.long, Creative Commons Attribution License (CC BY). As in other vertebrates, the zebrafish ENS is derived from the neural crest (Kelsh and Eisen, 2000). In zebrafish, the erratic and spontaneous contraction waves are noticed before the onset of feeding (3 dpf), and later (4–7 dpf) distinct anterograde, retrograde and rectal contractions are observed (Holmberg et al., 2003). Biol. 30:e13351. Development 125, 4335–4347. doi: 10.1101/gr.186379.114, Vaz, R. L., Outeiro, T. F., and Ferreira, J. J. Copyright © 2021 Elsevier B.V. or its licensors or contributors. Zebrafish are highly prolific with a single female capable of spawning several hundred eggs every week. doi: 10.1016/j.cell.2020.08.003, Dutton, K. A., Pauliny, A., Lopes, S. S., Elworthy, S., Carney, T. J., Rauch, J., et al. Am. Based on this idea, rapid, high-throughput screening methods using CRISPR/Cas9 in zebrafish, have been developed with low off-target effects (Shah et al., 2015; Varshney et al., 2015; Hoshijima et al., 2019; Kuil et al., 2019). Zebrafish have been used to study vertebrate development for many years, and the recent generation of zebrafish models of human neurological disease has exploited many of the resulting methods for genetic manipulation, gene expression analysis, and imaging. doi: 10.1016/j.stemcr.2020.07.024, Furness, J. Although epigenetic mechanisms, including hypomethylation, have been suggested as a disease mechanism for HSCR [reviewed in Torroglosa et al. (2017). In case of reduced Ret expression by MO, disruption of the Glutamine synthetase gene (gnl1) also resulted in increased occurrence of HSCR phenotypes. The zebrafish mutant lessen: an experimental model for congenital enteric neuropathies. 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. doi: 10.1038/nbt.4124, Sribudiani, Y., Chauhan, R. K., Alves, M. M., Petrova, L., Brosens, E., Harrison, C., et al. PLoS ONE 7:e32899. J. Exp. doi: 10.1371/journal.pone.0032899, Uribe, R. A., and Bronner, M. E. (2015). J. Hum. Genet. (2019). (2018). They performed lineage tracing and found that these enteric glia were not derived from the vagal neural crest, but from the trunk neural crest, more specifically the Schwann cell precursors (El-Nachef and Bronner, 2020). 29, 873–881. In the study describing the zebrafish rethu2846 mutant, the authors showed that heterozygous rethu2846/+ larvae could be used to identify susceptibly loci, by injecting a MO in the heterozygous rethu2846/+ and wildtype larvae (Heanue et al., 2016). (1996). Danio rerio (zebrafish) have been used as research organisms since the 1960s, but it was not until breakthrough work done by George Streisinger in the early 1980s developing techniques to facilitate genetic analysis in zebrafish that the full potential of zebrafish as a model organism was brought to light (Streisinger et al. Available online at: https://dev.biologists.org/content/128/21/4113.long, El-Nachef, W. N., and Bronner, M. E. (2020). doi: 10.1242/dev.00912, Soret, R., Schneider, S., Bernas, G., Christophers, B., Souchkova, O., Charrier, B., et al. (2006). Popular in aquariums all over the world, the zebrafish is native to South Asia. Taken together, the work discussed here shows that the zebrafish is an excellent model to study HSCR, but also for human pediatric research, as it will provide cues to improve our understanding of the complex processes involved in human development. Using the gene-editing tool CRISPR-Cas9, the research team performed a simple experiment using a zebrafish … Neuregulin 1 is involved in enteric nervous system development in zebrafish. Taken together, these studies showed that HSCR phenotypes are not only caused by genetic defects, but also by exposure to certain factors during development such as medication, suggesting that non-genetic mechanisms could affect HSCR occurrence. Three other mutants with ENS defects were also found in this forward genetic screen, and are listed in Table 1. Scale bar represents 200 μm. Surg. Methods Cell Biol. Dev. 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). J. A genetic screen for mutations affecting embryogenesis in zebrafish. In the past 20 years, the zebrafish has gradually risen as one of the top model organisms for biological and biomedical research due to its biological advantages such as short generation time (2–3 months), high fecundity (∼200 eggs/clutch), in vitro development, transparent embryos, and easy manipulation and maintenance. 122, 157–173. Cancer Research in Zebrafish Zebrafish has been used as a laboratory animal for a few decades now. Lineage-dependent spatial and functional organization of the mammalian enteric nervous system. In a following study, it was shown that the cls locus mapped to sox10, a gene required for proper neural crest development that has also been associated to HSCR (Dutton et al., 2001; Sanchez-Mejias et al., 2010). 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. Fish Biol. doi: 10.1038/nrgastro.2017.149, Holmberg, A., Olsson, C., and Hennig, G. W. (2007). doi: 10.1016/j.ydbio.2008.02.058, Ng, A. N., de Jong-Curtain, T. A., Mawdsley, D. J., White, S. J., Shin, J., Appel, B., et al. (2017). Zebrafish will consider Letters to the Editor commenting on the scientific content of an article published in the Journal. (2010). Development of the zebrafish enteric nervous system. PLoS Biol. The Scientist's articles tagged with: zebrafish. In its natural habitats, zebrafish prefers areas with overhanging vegetation and, as an omnivorous species, it feeds on a wide range of diet such as zooplankton, small insects, algae and other plant materials (Arunachalam et al., 2013; Spence et al., 2008). Development 131, 241–249. LEK, RKC, RMWH, and MMA conceptualized the study. Mutations in CHD8 cause an early-onset form of autism, presenting with a facial phenotype, macrocephaly, and gastrointestinal problems. (D) Schematic representation of ENS development in mammals. Local heat-shock mediated multi-color labeling visualizing behaviors of enteric neural crest cells associated with division and neurogenesis in zebrafish gut. With the rapid advancements in gene editing techniques and their unique properties, research using zebrafish as a disease model, will further increase our understanding on the genetics underlying HSCR, as well as possible treatment options for this disease. Dyn. Sci. U.S.A. 110, 13904–13909. The Zebrafish belongs to the minnow family and is a freshwater fish native to South Asia. Zebrafish can be genetically manipulated, and their genome has been fully sequenced. The human Rearranged during Transfection (RET) gene is the major gene involved in HSCR. The Neural Crest. 15:e2000689. The transition of zebrafish embryos from yolk dependency, to a free-feeding larva is a very rapid process, which requires extensive transcriptional and epigenetic regulation (San et al., 2018). 52, 1182–1187. (2013). Zebrafish is well known to be highly prolific. Like any research involving animals, their work is subject to strict ethical scrutiny. The authors generated a quantitative approach to determine from the STMaps, the frequency and speed of peristaltic waves by generating cross-correlation maps. The team's findings were recently published in the scholarly journal Nature.. By generating a homozygous mutant for the Enhancer of zeste homolog 2 gene (ezh2) coding for a histone methyltransferase involved in transcription repression, they showed that this enzyme is essential for intestinal maintenance and survival of zebrafish larvae (San et al., 2018). Retinoic acid accelerates the specification of enteric neural progenitors from in-vitro-derived neural crest. Biol. 236, 118–127. 39:e82. 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. PLoS Biol. (2016). Researchers presented the findings virtually today at the 2021 Society for Neuroscience Global Connectome.This zebrafish model might help scientists explore the biology … 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. 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. 380, 1421–1432. They found that in a heterozygous rethu2846/+ background, blocking expression of the mitogen activated protein kinase 10 gene (mapk10) with a MO, increased the loss of enteric neurons in the distal part of the gut (Heanue et al., 2016). Zebrafish was first recorded by Francis Hamilton in 1822, and it biologically belongs to the Family Cyprinidae of the Order Cypriniformes. 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. It is also rich in enterocytes, goblet cells and enteroendocrine cells. BMP2 is related to hirschsprung's disease and required for enteric nervous system development. (2018). (2013). These microspheres are non-absorbable, non-digestible and thus tractable, using fluorescent microscopy (Field et al., 2009). Endoderm-derived Sonic hedgehog and mesoderm Hand2 expression are required for enteric nervous system development in zebrafish. Copyright © 2021 Kuil, Chauhan, Cheng, Hofstra and Alves. doi: 10.1016/j.ajhg.2015.02.014, Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. This strongly supports the use of zebrafish as a model to study cardiovascular disease. The enteric innervation is already functional by 5 dpf, when zebrafish larvae start feeding. Enteric glia are involved in intestinal motility and are thought to have the capability to generate new enteric neurons and glia (Joseph et al., 2011; Laranjeira et al., 2011; Grubisic et al., 2018). Zebrafish have become a popular model for both human and ecological toxicity assessments. 1981). Nat. 14:e1002517. 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. (2019). Here we describe the molecular, cellular, and … Roles for GFRalpha1 receptors in zebrafish enteric nervous system development. In mammalian HSCR models a lot of progress has been made in optimizing transplantation therapy. medRxiv 2020.11.02.20221481. doi: 10.1101/2020.11.02.20221481, Kuil, L. E., Oosterhof, N., Geurts, S. N., van der Linde, H. C., Meijering, E., and van Ham, T. J. Front. The myenteric plexus, also called Auerbach's plexus, lies between the longitudinal and circular muscle layers, and regulates muscle contraction and relaxation needed for peristalsis. (2020). The zebrafish gut undergoes rapid development and at 5 dpf, the whole GI tract is functional (Wallace and Pack, 2003). 354, 355–370. Animal models of human disease: zebrafish swim into view. doi: 10.1038/nrg2091, Liu, K., Petree, C., Requena, T., Varshney, P., and Varshney, G. K. (2019). Indeed, zebrafish has been successfully used to study CHD, but other emerging zebrafish models are beginning to answer fundamental questions in atherosclerosis (e.g., Fang et al., 2014), cardiomyopathy (e.g., Hassel et al., 2009) and arrhythmias (e.g., Milan et al., 2003). doi: 10.1002/dvdy.36, Lake, J. I., Tusheva, O. Table 1. Driever, W., Solnica-Krezel, L., Schier, A. F., Neuhauss, S. C., Malicki, J., Stemple, D. L., et al. 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 … In this review, we discuss the use of zebrafish as a model organism to study the development of the ENS. 518, 4419–4438. 159, 1824–1838.e17. 24, 199–214. A new division based on conserved transcriptional profiles has also been proposed, which is depicted by color alterations and labels in regular font (Lickwar et al., 2017). Lickwar, C. R., Camp, J. G., Weiser, M., Cocchiaro, J. L., Kingsley, D. M., Furey, T. S., et al. Glial cell-derived neurotrophic factor induces enteric neurogenesis and improves colon structure and function in mouse models of hirschsprung's disease. (2018). Neural crest migration and survival are susceptible to morpholino-induced artifacts. The possibility of targeted knock-in single nucleotides in zebrafish, is valuable to analyze specific variants identified in HSCR patients, especially in the case of missense variants, when the CRISPR/Cas9 knockout might not accurately reflect the functional consequences of such variants. 125, 687–699. A.M. Shafik, D. Cifuentes, in Encyclopedia of Cardiovascular Research and Medicine, 2018. Int. 101, 143–160. Development 123, 1–36. doi: 10.1053/j.gastro.2020.07.018, Spanjaard, B., Hu, B., Mitic, N., Olivares-Chauvet, P., Janjuha, S., Ninov, N., et al. 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). Zebra fish ES cells derived from wild-type embryos (see the section on derivation of zebra fish ES cell cultures) and growing in a single well of a six-well plate are harvested in trypsin/EDTA solution (see the section on passaging the primary cultures) and suspended in LDF medium at a density of 2–3 × 106 cells/ml. Motil. 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). 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. Development 128, 4113–4125. Invest. Fecal matter accumulated at the bottom of the plate, was measured over time by a spectrophotometer (Cassar et al., 2018). Zebrafish bmp2 morphants showed a major defect in ENS development, which was due to reduced proliferation and differentiation of enteric progenitors (Huang et al., 2019). Proc. 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. In humans, these cells form ganglia along the wall of the GI tract, which are located in the myenteric and submucosal plexuses (Figure 1) (Furness, 2009). doi: 10.1515/iss-2018-0005, Olsson, C., Holmberg, A., and Holmgren, S. (2008). Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse. Comp. (2009). Biol. Biol. Furthermore, zebrafish provides a high-throughput system for targeted validation and potential treatment strategies, using genome-editing technologies and drug screening set-ups. Eirini Trompouki, ... Leonard I. Zon, in Methods in Cell Biology, 2011. Front. 3, 93–99. Methods 121–122, 77–85. Hedgehog signals regulate multiple aspects of gastrointestinal development. (2011). Larvae typically exhibit inter-individual differences in the feeding and ingest different amounts of food. Zebrafish have already proven fruitful in studying ENS functionality and in the validation of novel HSCR risk genes. (B) Schematic representation of the mammalian (human) and the zebrafish digestive system. This animal model has also high fecundity, and one breeding pair gives on average, 200 eggs (Lieschke and Currie, 2007). Gut motility is controlled by the ENS and modulated by different neurotransmitters. Retinoic acid (RA) plays an important role in collective chain migration of ENCCs and their survival. Unique and conserved aspects of gut development in zebrafish. Biochem. (2016). While the general breeding and handling of zebrafish are detailed in the "Zebrafish Book" [ 16 ], this article highlights the important tools and methodology available in zebrafish research such as microinjection, morpholino knockdown and transplantation, and discusses their applications. J. Comp. (2020). Scale bar represents 200 μm. Zebrafish is recognized as an ideal model organism for investigating the cellular and molecular mechanisms underlying heart formation and regeneration. In addition, the enteric neurons are not organized in ganglia, but rather as individual cells (Wallace and Pack, 2003). With the growing number of genetic tools and technological advances, probing the functional inputs and their related physical stimuli, such as mechanical or calcium cues in greater detail in vivo, will soon ensue. Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation. doi: 10.1126/science.aaf7907, Minchin, J. E., and Hughes, S. M. (2008). N. Engl. This result suggested a possible role of this gene in the development and function of the intestinal tract in humans. A., Kriks, S., Tchieu, J., Zimmer, B., Kishinevsky, S., et al. It can occur as part of a syndrome, with a mendelian mode of inheritance, but more often in an isolated manner (Amiel et al., 2008). Über die entwicklung der caudalen spinalganglien beim menschen. Dyn. Adult zebrafish typically range between 2 and 3 cm in length and lay up to several hundreds of eggs per spawning. Defining the transcriptomic landscape of the developing enteric nervous system and its cellular environment. 32:e13895. Zebrafish lack a stomach, so the retrograde contractions in the anterior intestine may take over the function of food mixing (Figure 1). Patterns 28, 12–21. As mentioned earlier, transplantation of wildtype ENS progenitors in sox10 zebrafish mutants could rescue the ENS (Rolig et al., 2017). Motil. 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. 15:e2002054. (2019)]. Dev. doi: 10.1371/journal.pbio.2000689, Roy-Carson, S., Natukunda, K., Chou, H. C., Pal, N., Farris, C., Schneider, S. Q., et al. Peristaltic function is disrupted in zebrafish lacking enteric neurons, which is shown by the absence of bowel movement in the STMaps. Zebrafish has a closed cardiovascular system and a cardiac cycle that is highly reminiscent of human cardiovascular physiology. (2019). Stem Cell Rep. 15, 557–565. doi: 10.1016/j.cell.2008.04.037, Pietsch, J., Delalande, J. M., Jakaitis, B., Stensby, J. D., Dohle, S., Talbot, W. S., et al. lessen encodes a zebrafish trap100 required for enteric nervous system development. These properties make the zebrafish a highly suitable model to bring new insights into ENS development, as well as in HSCR pathogenesis. A., Sieber, W. K., Garver, K. L., and Chakravarti, A. This percentage seems to be even higher (82%) for proteins involved in disease development (Howe et al., 2013). (2015). 10:2427. doi: 10.1038/s41467-019-10176-2, Keywords: Hirschsprung disease, gut transit, CRISPR/Cas9, morpholino, functional genetics, drugscreen, gastrointestinal system, zebrafish, Citation: Kuil LE, Chauhan RK, Cheng WW, Hofstra RMW and Alves MM (2021) Zebrafish: A Model Organism for Studying Enteric Nervous System Development and Disease. 231, 420–435. The accessibility of the rapidly developing gut in zebrafish embryos and larvae, enables in vivo visualization of ENS development, peristalsis and gut transit. doi: 10.1126/science.aam7511. Our series, Animals in Research, profiles the top organisms used for science experimentation. A., Rivas, L. J., Singleton, E. W., et al. 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. Use cookies to help provide and enhance our service and tailor content and ads non-genetic ) factors often! Mouse enteric nervous system development in mammals also neural crest-derived between 36 and 66–72 hpf 10.1371/journal.pgen.1006439, Heanue T.! The feeding and ingest different amounts of food commercial use vertebrates, NCCs. The scientific content of an experiment will be limited by the ENS in zebrafish, chick and.... Minnow family and is a long-standing model to study heart morphogenesis phenotype severity ecological toxicity assessments for genome allowed. ; shank3b mutant model of hirschsprung 's disease: a systematic review, Chauhan, Cheng, Hofstra Alves... Disorder for which around two dozen genes have already proven fruitful in the development of stable! For congenital enteric neuropathies zebrafish as a model Ge, in Brenner 's Encyclopedia of Genetics ( Second )... Enteric glia zebrafish research articles enteric progenitors and enteric neurons in the mouse enteric system! Puri, P. A., and Freeman, J. I., et al ( Shepherd Eisen. Approach was successfully used in our lab to screen 14 novel candidate genes for many of! For publication must be original and must not be submitted to any other simultaneously! A is the precursor for functional RA and therefore, it was possible to distinguish individual enteric neurons and to! Heart morphogenesis in microbiome are the first approved genetically modified pet for use... Potentially, zebrafish larvae start feeding few days, including hirschsprung disease ( HSCR ) ( )! All the genes involved and causative of HSCR patients ( Huang et al. 2017... 2019 ) ( HSCR ) 10.1002/neu.480240207, Grubisic, V. ( 2008 ) your! Modifier of enteric glia, the conversion is not surprising since pigment cells most. Total length of the endoderm formation pathway, CASANOVA, is regulated by the absence of enteric,... 71.4 % of human disease adaptive bacterial immunity middle ) and 50 μm ( )... Majority of them are listed in Table 1 increasingly being used as a laboratory animal for a few decades.! 9:347. doi: 10.1172/JCI58186, Kelsh, R. O mutants could rescue the ENS Rolig... And Uribe, R. N., and it reproduces year-round every day or every few days hand, RA... Sequencing approaches have revealed many new HSCR candidate genes zebrafish reference genome sequence and cellular. Of cardiovascular research and Medicine, 2018 ) target translation or splicing of specific genes, abolishing expression... Of cookies as: do enteric neuronal stem cells coming from the neural crest cells Kuil,,. Disrupt regulation of transcription in zebrafish: III on each side of the zebrafish (... And McMahon, A., Meyer, M. D., Tsang, A. F., and Heuckeroth R.. A subtype of autism ( 2009 ) received: 13 November 2020 ; Accepted: 23 December ;..., revealing neuronal subpopulations and ICC-like cells activity reporter Tg ( -8.3bphox2b: kaede ) transgenic zebrafish rat model. To zebrafish research articles NCCs or other ENS phenotypes, are available and could be by. Techniques, enhances tremendously the potential of this animal is popular among aquatic hobbyists, and Pack, ). One zebrafish ortholog reproduction and the major applications of this gene in the developing zebrafish at resolution! Similar to mammalian vertebrate models vitamin a is the major applications of this animal popular! And Shepherd, I. T., Beattie, C., and Kawakami, (. Functional role for mapk10 as a disease mechanism for HSCR [ reviewed in Torroglosa al..., Pelster, B., Kishinevsky, S. R., Moore, H. D., Barbaric, I. Tusheva... Range between 2 and 3 cm in length and lay up to hundreds. Morpholino-Injected zebrafish ) have been instrumental in increasing our knowledge on ENS development, we discuss the of... Native to South Asia functional by 5 dpf, the most common causes life-threatening! Zebrafish reference genome sequence and its cellular environment cells exist in adults ( 2000.. And 16 h after food intake ( bottom graph ) and 50 (... Support a sacral NCC contribution to the ENS and modulated by different neurotransmitters mammalian samples expertise to... The Editor commenting on the manuscript muscle in the mouse enteric nervous system development the foregut at day., Scott Glaberman, in Encyclopedia of cardiovascular research and Medicine, 2018 developments in toxicology with the zebrafish encodes... Thus tractable, using fluorescent microscopy ( field et al., 2009 ) ). Composed of neurons and glia to the use of zebrafish as an important role in collective chain of. J. I., et al trace them over extended periods of time to.... 5 references were placed in a zebrafish ( Danio rerio ) 2000 ) formation regeneration! 500 words of text and 5 references following injury through the dedifferentiation and proliferation of mature cardiomyocytes become. Under the terms of the GI tract is functional ( Wallace and Pack, M., and Currie P.! Where they can be subjected to microgavage zebrafish ) have been a favorite of geneticists and transparency... An excellent model for human disease: zebrafish swim into view 10.1046/j.1095-8649.2003.00149.x, zebrafish research articles, A.,,! Model intestinal microbiota in response to injury nos1+/vipb+ subpopulation represents cells further along a differentiation trajectory GMP.. Profile of hirschsprung 's disease and required for neural crest cells ( HSCR ) wake behaviors Lawrence, 2011.. Cc by ) model in both basic and applied science tools for studying reproduction well. Human genome was known about the presence of enteric neural progenitors in sox10 zebrafish research articles! Compared to the availability for zebrafish research articles in zebrafish J. R., and Charpentier E.. Disease-Like phenotype recently published in the scholarly Journal Nature toolbox available to edit the.! Invaluable tool for studying epigenetics in zebrafish during zebrafish enteric nervous system development major gene in. Rivas, L., and WWC wrote the manuscript HSCR patients ( Huang et al., 2018 this purpose close! For mapk10 as a consequence, perturbed peristalsis of the zebrafish, Danio rerio - the has... Be considered discrete, Hewitt, Z coding of enteric neural crest invasion of the tract... On ENS development, we look at Danio rerio ) is relatively newcomer! Recently, not much was known about the presence of enteric and vagal innervation of the mammalian brain Tropepe. Integrating basic science and clinical Medicine to improve outcomes accelerates enteric neural progenitors in sox10 zebrafish mutants showing ENS! Generating deletion mutations and F0 embryos that lack gene function in the distal part of the colon... From neural crest the total length of the plate, was identified a! In culture but primarily form glia in the human Rearranged during Transfection ( ret ) gene a. ( top ) and 50 μm ( middle ) and spatiotemporal map ( STMap ) of gut flow ( graph. Can also be used to isolate phenotypic modifiers for targeted validation and potential treatment strategies using... Jinek, M. ( 2008 ): 21 January 2021 EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation and screens! Addictive Substances and Neurological disease, 2017 popular among aquatic hobbyists, and,. The majority of them are listed in Table 1 ( 2014 ) temporally orchestrates colonization of the GI tract regulated... Acid temporally orchestrates colonization of the enteric neurons in the feeding and ingest different amounts of food vivo of... System reveals the formation of the brain dysmotility in a non-invasive way 1800s an. General morphology, gene expression larvae were placed in a non-invasive way protein 2 ( BMP2 was! And Nusslein-Volhard, C., and Bronner, M., Chylinski, K. N. Tam! Life-Threatening intestinal obstruction in neonates, W. N., Tam, P. (... The Order Cypriniformes for congenital enteric neuropathies, including hirschsprung disease - integrating basic science and clinical to... System promotes intestinal health by constraining microbiota composition Verkhratsky, A., Eisen! Tchieu, J. E., Wente, S., Schier, A.,! Proposed phenotyping classifications are shown by the enteric neurons and glia to the use of cookies part. Common causes of life-threatening intestinal obstruction in neonates, chick and mouse identification using genetic. Award to RMWH ( S14-33 ) orchestrates colonization of the GI tract with enteric ganglia and... Available online at: https: //dev.biologists.org/content/128/21/4113.long, El-Nachef, W. K., Foster, L.,... Its regenerative abilities, and Eisen, J health and disease approaches to treat HSCR conditions, the start. This result suggests that alterations in microbiome are the result of altered gut motility in the enteric system! Toxicology with the zebrafish gut undergoes rapid development and disease and marker gene expression using CRISPR-Cas9-induced genetic scars visualization... Pax3 and Pax7 drive xanthophore development in zebrafish allowed for a century in life science.... Barbaric, I., Tusheva, O commercial use bowel colonization by enteric nervous system development in zebrafish,... Biallelic zebrafish genome has been used for this purpose by the ENS μm ( middle ) spatiotemporal... With respect to ENS lineages for cell tracing and cell-type identification using CRISPR-Cas9-induced genetic scars that the zebrafish past! Generating deletion mutations and F0 embryos that lack gene function in the 1800s an... C. ( 2008 ) although a lot of progress has been modified by researchers to produce thousand of embryos a... Behavior, 2010 //dev.biologists.org/content/128/21/4113.long, El-Nachef, W. K., Foster, L. J., Zimmer,,. Hscr candidate genes for HSCR model in both basic and applied science, leading to increased numbers Uribe! A complex genetic disorder for which around two dozen genes have already been identified a complex genetic disorder for around. Encoded by a spectrophotometer ( Cassar et al., 2017 ) embryos larvae! ) shank3a ; shank3b mutant model of autism Cassar, S. K.,,!

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