Advertisement

Focusing the Spotlight on the Zebrafish Intestine to Illuminate Mechanisms of Colorectal Cancer

  • Viola H. Lobert
  • Dmitri Mouradov
  • Joan K. HeathEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 916)

Abstract

Colorectal cancer, encompassing colon and rectal cancer, arises from the epithelial lining of the large bowel. It is most prevalent in Westernised societies and is increasing in frequency as the world becomes more industrialised. Unfortunately, metastatic colorectal cancer is not cured by chemotherapy and the annual number of deaths caused by colorectal cancer, currently 700,000, is expected to rise. Our understanding of the contribution that genetic mutations make to colorectal cancer, although incomplete, is reasonably well advanced. However, it has only recently become widely appreciated that in addition to the ongoing accumulation of genetic mutations, chronic inflammation also plays a critical role in the initiation and progression of this disease. While a robust and tractable genetic model of colorectal cancer in zebrafish, suitable for pre-clinical studies, is not yet available, the identification of genes required for the rapid proliferation of zebrafish intestinal epithelial cells during development has highlighted a number of essential genes that could be targeted to disable colorectal cancer cells. Moreover, appreciation of the utility of zebrafish to study intestinal inflammation is on the rise. In particular, zebrafish provide unique opportunities to investigate the impact of genetic and environmental factors on the integrity of intestinal epithelial barrier function. With currently available tools, the interplay between epigenetic regulators, intestinal injury, microbiota composition and innate immune cell mobilisation can be analysed in exquisite detail. This provides excellent opportunities to define critical events that could potentially be targeted therapeutically. Further into the future, the use of zebrafish larvae as hosts for xenografts of human colorectal cancer tissue, while still in its infancy, holds great promise that zebrafish could one day provide a practical, preclinical personalized medicine platform for the rapid assessment of the metastatic potential and drug-sensitivity of patient-derived cancers.

Keywords

Zebrafish Intestinal epithelium Colon cancer Colorectal cancer WNT signalling Intestinal permeability Microbiota Inflammatory bowel disease 

Notes

Acknowledgements

The authors are immensely grateful to Drs Michael Christie, Jan Spitsbergen, Adam Parslow and Elizabeth Christie for kindly providing the images for Figs. 1, 3 and 4. Drs Karen Guillemin, Tanya de Jong-Curtain and Fansuo Geng are thanked for careful reading of the manuscript. Research in the Heath laboratory is supported by the National Health and Medical Research Council of Australia, Ludwig Cancer Research and operational infrastructure grants from the Australian Federal Government (IRISS) and the Victorian State Government (OIS). JKH wishes to thank all past and present members of her laboratory for contributing data and stimulating discussions on this topic over the past several years.

References

  1. 1.
    East JE, Saunders BP, Jass JR (2008) Sporadic and syndromic hyperplastic polyps and serrated adenomas of the colon: classification, molecular genetics, natural history, and clinical management. Gastroenterol Clin North Am 37(1):25–46, vPubMedCrossRefGoogle Scholar
  2. 2.
    Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337CrossRefGoogle Scholar
  3. 3.
    Hurlstone AF et al (2003) The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature 425(6958):633–637PubMedCrossRefGoogle Scholar
  4. 4.
    Haramis AP et al (2006) Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia. EMBO Rep 7(4):444–449PubMedPubMedCentralGoogle Scholar
  5. 5.
    International Agency for Research on Cancer (2014) In: Stewart BW, Wild CP (eds) World cancer report 2014. WHO, LyonGoogle Scholar
  6. 6.
    Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767PubMedCrossRefGoogle Scholar
  7. 7.
    Minoo P, Moyer MP, Jass JR (2007) Role of BRAF-V600E in the serrated pathway of colorectal tumourigenesis. J Pathol 212(2):124–133PubMedCrossRefGoogle Scholar
  8. 8.
    Fearon ER (2011) Molecular genetics of colorectal cancer. Annu Rev Pathol 6:479–507PubMedCrossRefGoogle Scholar
  9. 9.
    Koinuma K et al (2004) Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas. Int J Cancer 108(2):237–242PubMedCrossRefGoogle Scholar
  10. 10.
    Palles C et al (2013) Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 45(2):136–144PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Zhang B et al (2014) Proteogenomic characterization of human colon and rectal cancer. Nature 513(7518):382–387PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Isella C et al (2015) Stromal contribution to the colorectal cancer transcriptome. Nat Genet 47(4):312–319PubMedCrossRefGoogle Scholar
  13. 13.
    Washington MK et al (2013) Pathology of rodent models of intestinal cancer: progress report and recommendations. Gastroenterology 144(4):705–717PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Wallace KN et al (2005) Intestinal growth and differentiation in zebrafish. Mech Dev 122(2):157–173PubMedCrossRefGoogle Scholar
  15. 15.
    Noaillac-Depeyre J, Gas N (1976) Electron microscopic study on gut epithelium of the tench (Tinca tinca L.) with respect to its absorptive functions. Tissue Cell 8(3):511–530PubMedCrossRefGoogle Scholar
  16. 16.
    Wang Z et al (2010) Morphological and molecular evidence for functional organization along the rostrocaudal axis of the adult zebrafish intestine. BMC Genomics 11:392PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Vries RG, Huch M, Clevers H (2010) Stem cells and cancer of the stomach and intestine. Mol Oncol 4(5):373–384PubMedCrossRefGoogle Scholar
  18. 18.
    Crosnier C et al (2005) Delta-Notch signalling controls commitment to a secretory fate in the zebrafish intestine. Development 132(5):1093–1104PubMedCrossRefGoogle Scholar
  19. 19.
    Heath JK (2010) Transcriptional networks and signaling pathways that govern vertebrate intestinal development. Curr Top Dev Biol 90:159–192PubMedCrossRefGoogle Scholar
  20. 20.
    Crosnier C, Stamataki D, Lewis J (2006) Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat Rev Genet 7(5):349–359PubMedCrossRefGoogle Scholar
  21. 21.
    Cheesman SE et al (2011) Epithelial cell proliferation in the developing zebrafish intestine is regulated by the Wnt pathway and microbial signaling via Myd88. Proc Natl Acad Sci U S A 108(Suppl 1):4570–4577PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Muncan V et al (2007) T-cell factor 4 (Tcf7l2) maintains proliferative compartments in zebrafish intestine. EMBO Rep 8(10):966–973PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Faro A et al (2009) T-cell factor 4 (tcf7l2) is the main effector of Wnt signaling during zebrafish intestine organogenesis. Zebrafish 6(1):59–68PubMedCrossRefGoogle Scholar
  24. 24.
    Clevers H (2013) The intestinal crypt, a prototype stem cell compartment. Cell 154(2):274–284PubMedCrossRefGoogle Scholar
  25. 25.
    Philpott A, Winton DJ (2014) Lineage selection and plasticity in the intestinal crypt. Curr Opin Cell Biol 31:39–45PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Paquette CE et al (2013) A retrospective study of the prevalence and classification of intestinal neoplasia in zebrafish (Danio rerio). Zebrafish 10(2):228–236PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Cooper TK et al (2015) Primary intestinal and vertebral chordomas in laboratory zebrafish (Danio rerio). Vet Pathol 52:388–392PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Spitsbergen JM et al (2000) Neoplasia in zebrafish (Danio rerio) treated with 7,12-dimethylbenz[a]anthracene by two exposure routes at different developmental stages. Toxicol Pathol 28(5):705–715PubMedCrossRefGoogle Scholar
  29. 29.
    Reddy AP et al (1999) Experimental hepatic tumorigenicity by environmental hydrocarbon dibenzo[a, l]pyrene. J Environ Pathol Toxicol Oncol 18(4):261–269PubMedGoogle Scholar
  30. 30.
    Spitsbergen JM et al (2000) Neoplasia in zebrafish (Danio rerio) treated with N-methyl-N′-nitro-N-nitrosoguanidine by three exposure routes at different developmental stages. Toxicol Pathol 28(5):716–725PubMedCrossRefGoogle Scholar
  31. 31.
    Spitsbergen JM, Buhler DR, Peterson TS (2012) Neoplasia and neoplasm-associated lesions in laboratory colonies of zebrafish emphasizing key influences of diet and aquaculture system design. ILAR J 53(2):114–125PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kent ML et al (2002) Pseudocapillaria tomentosa, a nematode pathogen, and associated neoplasms of zebrafish (Danio rerio) kept in research colonies. Comp Med 52(4):354–358PubMedGoogle Scholar
  33. 33.
    Phelps RA et al (2009) A two-step model for colon adenoma initiation and progression caused by APC loss. Cell 137(4):623–634PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Hammoud SS, Cairns BR, Jones DA (2013) Epigenetic regulation of colon cancer and intestinal stem cells. Curr Opin Cell Biol 25(2):177–183PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Nadauld LD et al (2004) Adenomatous polyposis coli control of retinoic acid biosynthesis is critical for zebrafish intestinal development and differentiation. J Biol Chem 279(49):51581–51589PubMedCrossRefGoogle Scholar
  36. 36.
    Rai K et al (2010) DNA demethylase activity maintains intestinal cells in an undifferentiated state following loss of APC. Cell 142(6):930–942PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Yen J, White RM, Stemple DL (2014) Zebrafish models of cancer: progress and future challenges. Curr Opin Genet Dev 24:38–45PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Tobia C et al (2013) Zebrafish embryo as a tool to study tumor/endothelial cell cross-talk. Biochim Biophys Acta 1832(9):1371–1377PubMedCrossRefGoogle Scholar
  39. 39.
    White RM et al (2008) Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell 2(2):183–189PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Teng Y et al (2013) Evaluating human cancer cell metastasis in zebrafish. BMC Cancer 13:453PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Marques IJ et al (2009) Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model. BMC Cancer 9:128PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Lau T et al (2013) A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res 73(10):3132–3144PubMedCrossRefGoogle Scholar
  43. 43.
    Waaler J et al (2011) Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth. Cancer Res 71(1):197–205PubMedCrossRefGoogle Scholar
  44. 44.
    Weng W et al (2015) Molecular therapy of colorectal cancer: progress and future directions. Int J Cancer 136(3):493–502PubMedGoogle Scholar
  45. 45.
    Ng AN et al (2005) Formation of the digestive system in zebrafish: III. Intestinal epithelium morphogenesis. Dev Biol 286(1):114–135PubMedCrossRefGoogle Scholar
  46. 46.
    Mayer AN, Fishman MC (2003) Nil per os encodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish. Development 130(17):3917–3928PubMedCrossRefGoogle Scholar
  47. 47.
    de Jong-Curtain TA et al (2009) Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish. Gastroenterology 136(3):902–911PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Chen JN et al (1996) Mutations affecting the cardiovascular system and other internal organs in zebrafish. Development 123:293–302PubMedGoogle Scholar
  49. 49.
    Davuluri G et al (2008) Mutation of the zebrafish nucleoporin elys sensitizes tissue progenitors to replication stress. PLoS Genet 4(10), e1000240PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Pack M et al (1996) Mutations affecting development of zebrafish digestive organs. Development 123:321–328PubMedGoogle Scholar
  51. 51.
    Ober EA et al (2006) Mesodermal Wnt2b signalling positively regulates liver specification. Nature 442(7103):688–691PubMedCrossRefGoogle Scholar
  52. 52.
    Field HA et al (2003) Formation of the digestive system in zebrafish. I. Liver morphogenesis. Dev Biol 253(2):279–290PubMedCrossRefGoogle Scholar
  53. 53.
    Ober EA, Field HA, Stainier DY (2003) From endoderm formation to liver and pancreas development in zebrafish. Mech Dev 120(1):5–18PubMedCrossRefGoogle Scholar
  54. 54.
    Field HA et al (2003) Formation of the digestive system in zebrafish. II. Pancreas morphogenesis. Dev Biol 261(1):197–208PubMedCrossRefGoogle Scholar
  55. 55.
    Boglev Y et al (2013) Autophagy induction is a Tor- and Tp53-independent cell survival response in a zebrafish model of disrupted ribosome biogenesis. PLoS Genet 9(2), e1003279PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Markmiller S et al (2014) Minor class splicing shapes the zebrafish transcriptome during development. Proc Natl Acad Sci U S A 111(8):3062–3067PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Wang Y et al (2012) Ribosome biogenesis factor Bms1-like is essential for liver development in zebrafish. J Genet Genomics 39(9):451–462PubMedCrossRefGoogle Scholar
  58. 58.
    Hutchinson SA et al (2012) Tbl3 regulates cell cycle length during zebrafish development. Dev Biol 368(2):261–272PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Hozumi S et al (2012) DEAD-box protein Ddx46 is required for the development of the digestive organs and brain in zebrafish. PLoS One 7(3), e33675PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Yee NS et al (2007) Mutation of RNA Pol III subunit rpc2/polr3b leads to deficiency of subunit Rpc11 and disrupts zebrafish digestive development. PLoS Biol 5(11), e312PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Berghmans S et al (2005) tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. Proc Natl Acad Sci U S A 102(2):407–412PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Bywater MJ et al (2012) Inhibition of RNA polymerase I as a therapeutic strategy to promote cancer-specific activation of p53. Cancer Cell 22(1):51–65PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Wallace KN et al (2005) Mutation of smooth muscle myosin causes epithelial invasion and cystic expansion of the zebrafish intestine. Dev Cell 8(5):717–726PubMedCrossRefGoogle Scholar
  64. 64.
    Alhopuro P et al (2008) Unregulated smooth-muscle myosin in human intestinal neoplasia. Proc Natl Acad Sci U S A 105(14):5513–5518PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Itzkowitz SH, Yio X (2004) Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 287(1):G7–G17PubMedCrossRefGoogle Scholar
  66. 66.
    Clevers H (2004) At the crossroads of inflammation and cancer. Cell 118(6):671–674PubMedCrossRefGoogle Scholar
  67. 67.
    Kim ER, Chang DK (2014) Colorectal cancer in inflammatory bowel disease: the risk, pathogenesis, prevention and diagnosis. World J Gastroenterol 20(29):9872–9881PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Alonso A et al (2015) Identification of risk loci for Crohn’s disease phenotypes using a genome-wide association study. Gastroenterology 148:794–805PubMedCrossRefGoogle Scholar
  69. 69.
    Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678Google Scholar
  70. 70.
    Anderson CA et al (2011) Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43(3):246–252PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Franke A et al (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 42(12):1118–1125PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Mathew CG (2008) New links to the pathogenesis of Crohn disease provided by genome-wide association scans. Nat Rev Genet 9(1):9–14PubMedCrossRefGoogle Scholar
  73. 73.
    Marjoram L et al (2015) Epigenetic control of intestinal barrier function and inflammation in zebrafish. Proc Natl Acad Sci U S A 112(9):2770–2775PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Thakur PC et al (2014) Dysregulated phosphatidylinositol signaling promotes endoplasmic-reticulum-stress-mediated intestinal mucosal injury and inflammation in zebrafish. Dis Model Mech 7(1):93–106PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Witte M et al (2014) Deficiency in macrophage-stimulating protein results in spontaneous intestinal inflammation and increased susceptibility toward epithelial damage in zebrafish. Zebrafish 11(6):542–550PubMedCrossRefGoogle Scholar
  76. 76.
    Oehlers SH et al (2011) A chemical enterocolitis model in zebrafish larvae that is dependent on microbiota and responsive to pharmacological agents. Dev Dyn 240(1):288–298PubMedCrossRefGoogle Scholar
  77. 77.
    Oehlers SH et al (2013) Chemically induced intestinal damage models in zebrafish larvae. Zebrafish 10(2):184–193PubMedCrossRefGoogle Scholar
  78. 78.
    He Q et al (2014) Role of gut microbiota in a zebrafish model with chemically induced enterocolitis involving toll-like receptor signaling pathways. Zebrafish 11(3):255–264PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Oehlers SH et al (2012) Retinoic acid suppresses intestinal mucus production and exacerbates experimental enterocolitis. Dis Model Mech 5(4):457–467PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Gersemann M et al (2009) Differences in goblet cell differentiation between Crohn’s disease and ulcerative colitis. Differentiation 77(1):84–94PubMedCrossRefGoogle Scholar
  81. 81.
    Kulaylat MN, Dayton MT (2010) Ulcerative colitis and cancer. J Surg Oncol 101(8):706–712PubMedCrossRefGoogle Scholar
  82. 82.
    Feng Y et al (2010) Live imaging of innate immune cell sensing of transformed cells in zebrafish larvae: parallels between tumor initiation and wound inflammation. PLoS Biol 8(12), e1000562PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Feng Y, Renshaw S, Martin P (2012) Live imaging of tumor initiation in zebrafish larvae reveals a trophic role for leukocyte-derived PGE(2). Curr Biol 22(13):1253–1259PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Langley RE, Rothwell PM (2014) Aspirin in gastrointestinal oncology: new data on an old friend. Curr Opin Oncol 26(4):441–447PubMedCrossRefGoogle Scholar
  85. 85.
    Mione M, Zon LI (2012) Cancer and inflammation: an aspirin a day keeps the cancer at bay. Curr Biol 22(13):R522–R525PubMedCrossRefGoogle Scholar
  86. 86.
    Neufert C, Becker C, Neurath MF (2007) An inducible mouse model of colon carcinogenesis for the analysis of sporadic and inflammation-driven tumor progression. Nat Protoc 2(8):1998–2004PubMedCrossRefGoogle Scholar
  87. 87.
    Rawls JF et al (2006) Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection. Cell 127(2):423–433PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Kanther M et al (2011) Microbial colonization induces dynamic temporal and spatial patterns of NF-kappaB activation in the zebrafish digestive tract. Gastroenterology 141(1):197–207PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Bates JM et al (2007) Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host Microbe 2(6):371–382PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Galindo-Villegas J et al (2012) Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development. Proc Natl Acad Sci U S A 109(39):E2605–E2614PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Rawls JF, Samuel BS, Gordon JI (2004) Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota. Proc Natl Acad Sci U S A 101(13):4596–4601PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Cocchiaro JL, Rawls JF (2013) Microgavage of zebrafish larvae. J Vis Exp 72, e4434PubMedGoogle Scholar
  93. 93.
    Ellett F et al (2011) mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish. Blood 117(4):e49–e56PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Renshaw SA et al (2006) A transgenic zebrafish model of neutrophilic inflammation. Blood 108(13):3976–3978PubMedCrossRefGoogle Scholar
  95. 95.
    Bates JM et al (2006) Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol 297(2):374–386PubMedCrossRefGoogle Scholar
  96. 96.
    Jemielita M et al (2014) Spatial and temporal features of the growth of a bacterial species colonizing the zebrafish gut. MBio 5(6)Google Scholar
  97. 97.
    Roeselers G et al (2011) Evidence for a core gut microbiota in the zebrafish. ISME J 5(10):1595–1608PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    He Q et al (2013) Microbial fingerprinting detects intestinal microbiota dysbiosis in Zebrafish models with chemically-induced enterocolitis. BMC Microbiol 13:289PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Bongers G et al (2014) Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice. J Exp Med 211(3):457–472PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Jobin C (2014) Do bugs define cancer geography? J Exp Med 211(3):385PubMedCrossRefGoogle Scholar
  101. 101.
    Flasse LC et al (2013) The bHLH transcription factor Ascl1a is essential for the specification of the intestinal secretory cells and mediates Notch signaling in the zebrafish intestine. Dev Biol 376(2):187–197PubMedCrossRefGoogle Scholar
  102. 102.
    Roach G et al (2013) Loss of ascl1a prevents secretory cell differentiation within the zebrafish intestinal epithelium resulting in a loss of distal intestinal motility. Dev Biol 376(2): 171–186PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Navis A, Marjoram L, Bagnat M (2013) Cftr controls lumen expansion and function of Kupffer’s vesicle in zebrafish. Development 140(8):1703–1712PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Stuckenholz C et al (2009) FACS-assisted microarray profiling implicates novel genes and pathways in zebrafish gastrointestinal tract development. Gastroenterology 137(4):1321–1332PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Tao T et al (2013) Def functions as a cell autonomous factor in organogenesis of digestive organs in zebrafish. PLoS One 8(4), e58858PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Shepard JL et al (2007) A mutation in separase causes genome instability and increased susceptibility to epithelial cancer. Genes Dev 21(1):55–59PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Itoh M et al (2003) Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell 4(1):67–82PubMedCrossRefGoogle Scholar
  108. 108.
    Seiler C et al (2012) Smooth muscle tension induces invasive remodeling of the zebrafish intestine. PLoS Biol 10(9), e1001386PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Zheng X et al (2012) Loss of zygotic NUP107 protein causes missing of pharyngeal skeleton and other tissue defects with impaired nuclear pore function in zebrafish embryos. J Biol Chem 287(45):38254–38264PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Horne-Badovinac S et al (2001) Positional cloning of heart and soul reveals multiple roles for PKC lambda in zebrafish organogenesis. Curr Biol 11(19):1492–1502PubMedCrossRefGoogle Scholar
  111. 111.
    Yang J et al (2009) hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. PLoS Genet 5(2):e1000363Google Scholar
  112. 112.
    Lorenzen JA et al (2005) Rbm19 is a nucleolar protein expressed in crypt/progenitor cells of the intestinal epithelium. Gene Expr Patterns 6(1):45–56PubMedCrossRefGoogle Scholar
  113. 113.
    Niu X et al (2012) Sec13 safeguards the integrity of the endoplasmic reticulum and organogenesis of the digestive system in zebrafish. Dev Biol 367(2):197–207PubMedCrossRefGoogle Scholar
  114. 114.
    Alvers AL et al (2014) Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling. Development 141(5):1110–1119PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    van der Velden YU et al (2011) The serine-threonine kinase LKB1 is essential for survival under energetic stress in zebrafish. Proc Natl Acad Sci U S A 108(11):4358–4363PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Bagnat M et al (2007) Genetic control of single lumen formation in the zebrafish gut. Nat Cell Biol 9(8):954–960PubMedCrossRefGoogle Scholar
  117. 117.
    Sun Z, Hopkins N (2001) vhnf1, the MODY5 and familial GCKD-associated gene, regulates regional specification of the zebrafish gut, pronephros, and hindbrain. Genes Dev 15(23):3217–3229PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Ho SY et al (2006) Zebrafish fat-free is required for intestinal lipid absorption and Golgi apparatus structure. Cell Metab 3(4):289–300PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Viola H. Lobert
    • 1
    • 2
  • Dmitri Mouradov
    • 3
  • Joan K. Heath
    • 1
    • 4
    Email author
  1. 1.Development and Cancer DivisionThe Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  2. 2.Department of Biochemistry, Institute for Cancer ResearchOslo University Hospital, MontebelloOsloNorway
  3. 3.Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  4. 4.Department of Medical BiologyUniversity of MelbourneParkvilleAustralia

Personalised recommendations