Epigenetic mechanisms in hirschsprung disease. The zebrafish transcriptome shows overlap with the human and mouse ENS single-cell transcriptome (Drokhlyansky et al., 2020), for example, with regard to the presence of various enteric neuronal subtypes. X.-X.I. Development 125, 4335–4347. 433, 17–32. Wei Ge, in Encyclopedia of Reproduction (Second Edition), 2018. Such approach was successfully used in our lab to screen 14 novel candidate genes for HSCR. 3, 93–99. Therefore, a pre-sorting is warranted to reduce variability. Think I missed one? 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. Overview of the stable zebrafish mutants and morphants presenting an ENS phenotype. Baker, P. A., Meyer, M. D., Tsang, A., and Uribe, R. A. (1996). doi: 10.1016/S1095-6433(00)00330-5, Orts Llorca, F. (1934). doi: 10.1016/S0012-1606(02)00034-9, Wang, X., Chan, A. K., Sham, M. H., Burns, A. J., and Chan, W. Y. Involvement of SOX10 in the pathogenesis of Hirschsprung disease: report of a truncating mutation in an isolated patient. Dyn. 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. Development 127, 2763–2772. doi: 10.1002/cne.21705, Olsson, C., and Holmgren, S. (2001). 255, 12–29. (A) Schematic representation of the layers present in the GI tract of mammalians and zebrafish. Zebrafish Research. doi: 10.1016/j.ydbio.2015.09.023, Shah, A. N., Davey, C. F., Whitebirch, A. C., Miller, A. C., and Moens, C. B. Also, the expression of various HSCR-causing genes including the Rearranged during transfection (ret), GDNF family receptor alpha 1 (gfra1) and zinc finger E-box binding homeobox (zeb2), is conserved (Roy-Carson et al., 2017). (2020). Nature 556, 108–112. Nat. Zebrafish are increasingly being used as a model system for understanding the genetic and neuronal basis of behavior. Along with mice and humans, they are one of the most commonly studied animals in biomedical research. 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. 31, 701–710. Zebrafish are becoming more and more popular as a research model for human 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. 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). doi: 10.1371/journal.pone.0167278, Bonora, E., Bianco, F., Cordeddu, L., Bamshad, M., Francescatto, L., Dowless, D., et al. (2013). A., Kriks, S., Tchieu, J., Zimmer, B., Kishinevsky, S., et al. doi: 10.1016/j.ajhg.2015.02.014, Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. doi: 10.1053/j.gastro.2020.07.018, Spanjaard, B., Hu, B., Mitic, N., Olivares-Chauvet, P., Janjuha, S., Ninov, N., et al. 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. They shed light on the transcriptomes of enteric NCCs transforming into enteric neurons, and showed conserved enteric programs (Lasrado et al., 2017; Howard et al., 2020). 18:48. doi: 10.1186/s13059-017-1174-6. During a chemical screening in cultured human ENCCs, pepstatin A was discovered to be capable of improving colonization of transplanted NCCs in vitro and in vivo (Fattahi et al., 2016). Dev. (2015). 31, 227–229. Due to recent technical advances, including genome editing, lineage tracing, optogenetics, and in vivo imaging, the zebrafish gained popularity as a model for basic research, as well as for disease modeling, in a wide variety of research topics (Lieschke and Currie, 2007). J. Exp. The human and mouse enteric nervous system at single-cell resolution. Expression of bone morphogenic protein 2 (BMP2) was found reduced in intestines of HSCR patients (Huang et al., 2019). Motil. 292, 174–188. The zebrafish transcriptome of the developing ENS, has been determined by bulk RNA sequencing of neural and non-neural crest cells isolated from 7 dpf zebrafish intestines (Roy-Carson et al., 2017). Contribution of rare and common variants determine complex diseases-Hirschsprung disease as a model. 15:e2002054. LEK, RKC, and WWC wrote the manuscript. In the uhrf1 mutant fish, ENS progenitor transplantation from wildtype donors was used to test cell autonomous effects (Ganz et al., 2019). 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. doi: 10.1007/s00441-004-1023-2, Wallace, K. N., Akhter, S., Smith, E. M., Lorent, K., and Pack, M. (2005). Proc. 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. Van Nassauw, Neurochemical coding of enteric neurons in adult and embryonic zebrafish (Danio rerio). NCCs migrate in two parallel chains caudally, between 36 and 66–72 hpf. Dev. doi: 10.1016/j.gep.2018.01.003, Obermayr, F., and Seitz, G. (2018). doi: 10.1101/406553, Kuwata, M., Nikaido, M., and Hatta, K. (2019). Detection of enteric neural crest cells (ENCCs) and enteric neurons in zebrafish, is the vital first step to study ENS development and defects herein. (2009). Making waves: new developments in toxicology with the zebrafish. Recent developments in cell-based ENS regeneration - a short review. Ontogeny of intestinal motility in correlation to neuronal development in zebrafish embryos and larvae. Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation.
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. Integr. View all