Male-biased aganglionic megacolon in the TashT mouse model of Hirschsprung disease involves upregulation of p53 protein activity and Ddx3y gene expression


Autoři: Tatiana Cardinal aff001;  Karl-Frédérik Bergeron aff002;  Rodolphe Soret aff001;  Ouliana Souchkova aff001;  Christophe Faure aff002;  Amélina Guillon aff001;  Nicolas Pilon aff001
Působiště autorů: Molecular Genetics of Development Laboratory, Département des Sciences Biologiques, Université du Québec à Montréal (UQAM), Montréal, Québec, Canada aff001;  Centre d’excellence en recherche sur les maladies orphelines–Fondation Courtois (CERMO-FC), Université du Québec à Montréal, Montréal, Québec, Canada aff002;  Lipid Metabolism Laboratory, Département des Sciences Biologiques, Université du Québec à Montréal (UQAM), Montréal, Québec, Canada aff003;  Département de pédiatrie, Université de Montréal, Montréal, Québec, Canada aff004;  Division de gastroentérologie, hépatologie et nutrition pédiatrique, Centre hospitalier universitaire Sainte-Justine, Montréal, Québec, Canada aff005
Vyšlo v časopise: Male-biased aganglionic megacolon in the TashT mouse model of Hirschsprung disease involves upregulation of p53 protein activity and Ddx3y gene expression. PLoS Genet 16(9): e32767. doi:10.1371/journal.pgen.1009008
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009008

Souhrn

Hirschsprung disease (HSCR) is a complex genetic disorder of neural crest development resulting in incomplete formation of the enteric nervous system (ENS). This life-threatening neurocristopathy affects 1/5000 live births, with a currently unexplained male-biased ratio. To address this lack of knowledge, we took advantage of the TashT mutant mouse line, which is the only HSCR model to display a robust male bias. Our prior work revealed that the TashT insertional mutation perturbs a Chr.10 silencer-enriched non-coding region, leading to transcriptional dysregulation of hundreds of genes in neural crest-derived ENS progenitors of both sexes. Here, through sex-stratified transcriptome analyses and targeted overexpression in ENS progenitors, we show that male-biased ENS malformation in TashT embryos is not due to upregulation of Sry–the murine ortholog of a candidate gene for the HSCR male bias in humans–but instead involves upregulation of another Y-linked gene, Ddx3y. This discovery might be clinically relevant since we further found that the DDX3Y protein is also expressed in the ENS of a subset of male HSCR patients. Mechanistically, other data including chromosome conformation captured-based assays and CRISPR/Cas9-mediated deletions suggest that Ddx3y upregulation in male TashT ENS progenitors is due to increased transactivation by p53, which appears especially active in these cells yet without triggering apoptosis. Accordingly, in utero treatment of TashT embryos with the p53 inhibitor pifithrin-α decreased Ddx3y expression and abolished the otherwise more severe ENS defect in TashT males. Our data thus highlight novel pathogenic roles for p53 and DDX3Y during ENS formation in mice, a finding that might help to explain the intriguing male bias of HSCR in humans.

Klíčová slova:

Colon – Gene expression – Genetically modified animals – Mouse models – Neurons – Y-linked traits – Hirschsprung disease – Megacolon


Zdroje

1. Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G, Borrego S, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008;45(1):1–14. Epub 2007/10/30. jmg.2007.053959 [pii] doi: 10.1136/jmg.2007.053959 17965226.

2. Heuckeroth RO. Hirschsprung disease—integrating basic science and clinical medicine to improve outcomes. Nat Rev Gastroenterol Hepatol. 2018;15(3):152–67. doi: 10.1038/nrgastro.2017.149 29300049.

3. Pini Prato A, Gentilino V, Giunta C, Avanzini S, Mattioli G, Parodi S, et al. Hirschsprung disease: do risk factors of poor surgical outcome exist? J Pediatr Surg. 2008;43(4):612–9. Epub 2008/04/15. doi: 10.1016/j.jpedsurg.2007.10.007 18405705.

4. Bergeron KF, Silversides DW, Pilon N. The developmental genetics of Hirschsprung's disease. Clin Genet. 2013;83(1):15–22. Epub 2012/10/10. doi: 10.1111/cge.12032 23043324.

5. Nagy N, Goldstein AM. Enteric nervous system development: A crest cell's journey from neural tube to colon. Semin Cell Dev Biol. 2017;66:94–106. Epub 2017/01/15. doi: 10.1016/j.semcdb.2017.01.006 28087321; PubMed Central PMCID: PMC5474363.

6. Rao M, Gershon MD. Enteric nervous system development: what could possibly go wrong? Nat Rev Neurosci. 2018;19(9):552–65. Epub 2018/07/27. doi: 10.1038/s41583-018-0041-0 30046054.

7. Yntema CL, Hammond WS. The origin of intrinsic ganglia of trunk viscera from vagal neural crest in the chick embryo. J Comp Neurol. 1954;101(2):515–41. Epub 1954/10/01. 13221667.

8. Espinosa-Medina I, Jevans B, Boismoreau F, Chettouh Z, Enomoto H, Muller T, et al. Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest. Proc Natl Acad Sci U S A. 2017;114(45):11980–5. Epub 2017/10/29. doi: 10.1073/pnas.1710308114 29078343; PubMed Central PMCID: PMC5692562.

9. Le Douarin NM, Teillet MA. The migration of neural crest cells to the wall of the digestive tract in avian embryo. Journal of embryology and experimental morphology. 1973;30(1):31–48. Epub 1973/08/01. 4729950.

10. Uesaka T, Nagashimada M, Enomoto H. Neuronal Differentiation in Schwann Cell Lineage Underlies Postnatal Neurogenesis in the Enteric Nervous System. J Neurosci. 2015;35(27):9879–88. doi: 10.1523/JNEUROSCI.1239-15.2015 26156989.

11. Burns AJ, Champeval D, Le Douarin NM. Sacral neural crest cells colonise aganglionic hindgut in vivo but fail to compensate for lack of enteric ganglia. Dev Biol. 2000;219(1):30–43. 10677253.

12. Tang CSM, Zhuang X, Lam W-Y, Ngan ES-W, Hsu JS, Michelle YU, et al. Uncovering the genetic lesions underlying the most severe form of Hirschsprung disease by whole-genome sequencing. European Journal of Human Genetics. 2018;26(6):818–26. doi: 10.1038/s41431-018-0129-z

13. Tang CS-m, Li P, Lai FP-L, Fu AX, Lau S-T, So MT, et al. Identification of genes associated with Hirschsprung disease, based on whole-genome sequence analysis, and potential effects on enteric nervous system development. Gastroenterology. 2018;155(6):1908–22.e5. https://doi.org/10.1053/j.gastro.2018.09.012.

14. Tilghman JM, Ling AY, Turner TN, Sosa MX, Krumm N, Chatterjee S, et al. Molecular genetic anatomy and risk profile of Hirschsprung’s disease. New England Journal of Medicine. 2019;380(15):1421–32. doi: 10.1056/NEJMoa1706594

15. Gui H, Schriemer D, Cheng WW, Chauhan RK, Antiňolo G, Berrios C, et al. Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes. Genome Biology. 2017;18(1):48. doi: 10.1186/s13059-017-1174-6

16. Cantrell VA, Owens SE, Chandler RL, Airey DC, Bradley KM, Smith JR, et al. Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease. Hum Mol Genet. 2004;13(19):2289–301. doi: 10.1093/hmg/ddh243 15294878.

17. Dang R, Torigoe D, Suzuki S, Kikkawa Y, Moritoh K, Sasaki N, et al. Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations. PLoS ONE. 2011;6(9):e24086. Epub 2011/09/15. doi: 10.1371/journal.pone.0024086 PONE-D-11-10786 [pii]. 21915282; PubMed Central PMCID: PMC3168492.

18. McCallion AS, Stames E, Conlon RA, Chakravarti A. Phenotype variation in two-locus mouse models of Hirschsprung disease: tissue-specific interaction between Ret and Ednrb. Proc Natl Acad Sci U S A. 2003;100(4):1826–31. 12574515.

19. Uesaka T, Nagashimada M, Yonemura S, Enomoto H. Diminished Ret expression compromises neuronal survival in the colon and causes intestinal aganglionosis in mice. J Clin Invest. 2008;118(5):1890–8. Epub 2008/04/17. doi: 10.1172/JCI34425 18414682; PubMed Central PMCID: PMC2293334.

20. Vohra BP, Planer W, Armon J, Fu M, Jain S, Heuckeroth RO. Reduced endothelin converting enzyme-1 and endothelin-3 mRNA in the developing bowel of male mice may increase expressivity and penetrance of Hirschsprung disease-like distal intestinal aganglionosis. Dev Dyn. 2007;236(1):106–17. doi: 10.1002/dvdy.21028 17131407.

21. Okamoto N, Del Maestro R, Valero R, Monros E, Poo P, Kanemura Y, et al. Hydrocephalus and Hirschsprung's disease with a mutation of L1CAM. J Hum Genet. 2004;49(6):334–7. Epub 2004/05/19. doi: 10.1007/s10038-004-0153-4 15148591.

22. Parisi MA, Kapur RP, Neilson I, Hofstra RM, Holloway LW, Michaelis RC, et al. Hydrocephalus and intestinal aganglionosis: is L1CAM a modifier gene in Hirschsprung disease? Am J Med Genet. 2002;108(1):51–6. Epub 2002/02/22. doi: 10.1002/ajmg.10185 [pii]. 11857550.

23. Fransen E, Lemmon V, Van Camp G, Vits L, Coucke P, Willems PJ. CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1. Eur J Hum Genet. 1995;3(5):273–84. Epub 1995/01/01. 8556302.

24. Wallace AS, Tan MX, Schachner M, Anderson RB. L1cam acts as a modifier gene for members of the endothelin signalling pathway during enteric nervous system development. Neurogastroenterol Motil. 2011;23(11):e510–22. Epub 2011/03/15. doi: 10.1111/j.1365-2982.2011.01692.x 21395909.

25. Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R. Male development of chromosomally female mice transgenic for Sry. Nature. 1991;351(6322):117–21. Epub 1991/05/09. doi: 10.1038/351117a0 2030730.

26. Lee J, Harley VR. The male fight-flight response: A result of SRY regulation of catecholamines? BioEssays. 2012;34(6):454–7. doi: 10.1002/bies.201100159

27. Lee J, Pinares-Garcia P, Loke H, Ham S, Vilain E, Harley VR. Sex-specific neuroprotection by inhibition of the Y-chromosome gene, SRY, in experimental Parkinson's disease. Proc Natl Acad Sci U S A. 2019. Epub 2019/08/03. doi: 10.1073/pnas.1900406116 31371505.

28. Boyer A, Pilon N, Raiwet DL, Lussier JG, Silversides DW. Human and pig SRY 5' flanking sequences can direct reporter transgene expression to the genital ridge and to migrating neural crest cells. Dev Dyn. 2006;235(3):623–32. 16411204.

29. Bergeron KF, Cardinal T, Toure AM, Beland M, Raiwet DL, Silversides DW, et al. Male-Biased Aganglionic Megacolon in the TashT Mouse Line Due to Perturbation of Silencer Elements in a Large Gene Desert of Chromosome 10. PLoS Genet. 2015;11(3):e1005093. doi: 10.1371/journal.pgen.1005093 25786024.

30. Li Y, Kido T, Garcia-Barcelo MM, Tam PK, Tabatabai ZL, Lau YF. SRY interference of normal regulation of the RET gene suggests a potential role of the Y-chromosome gene in sexual dimorphism in Hirschsprung disease. Hum Mol Genet. 2015;24(3):685–97. doi: 10.1093/hmg/ddu488 25267720; PubMed Central PMCID: PMC4291247.

31. Bergeron KF, Nguyen CM, Cardinal T, Charrier B, Silversides DW, Pilon N. Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of waardenburg syndrome type 4. Disease models & mechanisms. 2016;9(11):1283–93. Epub Sep 1. doi: 10.1242/dmm.026773 27585883.

32. Soret R, Mennetrey M, Bergeron KF, Dariel A, Neunlist M, Grunder F, et al. A collagen VI-dependent pathogenic mechanism for Hirschsprung's disease. J Clin Invest. 2015;125(12):4483–96. doi: 10.1172/JCI83178 26571399.

33. Cheng LS, Schwartz DM, Hotta R, Graham HK, Goldstein AM. Bowel dysfunction following pullthrough surgery is associated with an overabundance of nitrergic neurons in Hirschsprung disease. J Pediatr Surg. 2016;51(11):1834–8. doi: 10.1016/j.jpedsurg.2016.08.001 27570241; PubMed Central PMCID: PMC5065396.

34. Toure AM, Charrier B, Pilon N. Male-specific colon motility dysfunction in the TashT mouse line. Neurogastroenterol Motil. 2016;28(10):1494–507. doi: 10.1111/nmo.12847 27278627.

35. Zaitoun I, Erickson CS, Barlow AJ, Klein TR, Heneghan AF, Pierre JF, et al. Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprung's disease. Neurogastroenterol Motil. 2013;25(3):e233–44. doi: 10.1111/nmo.12083 23360229; PubMed Central PMCID: PMC3578114.

36. Pierre JF, Barlow-Anacker AJ, Erickson CS, Heneghan AF, Leverson GE, Dowd SE, et al. Intestinal dysbiosis and bacterial enteroinvasion in a murine model of Hirschsprung's disease. J Pediatr Surg. 2014;49(8):1242–51. doi: 10.1016/j.jpedsurg.2014.01.060 25092084; PubMed Central PMCID: PMC4122863.

37. Toure AM, Landry M, Souchkova O, Kembel SW, Pilon N. Gut microbiota-mediated Gene-Environment interaction in the TashT mouse model of Hirschsprung disease. Scientific reports. 2019;9(1):492. Epub 2019/01/27. doi: 10.1038/s41598-018-36967-z 30679567.

38. Ward NL, Pieretti A, Dowd SE, Cox SB, Goldstein AM. Intestinal aganglionosis is associated with early and sustained disruption of the colonic microbiome. Neurogastroenterol Motil. 2012;24(9):874–e400. doi: 10.1111/j.1365-2982.2012.01937.x 22626027.

39. Pilon N. Pigmentation-based insertional mutagenesis is a simple and potent screening approach for identifying neurocristopathy-associated genes in mice. Rare Diseases. 2016;4(1):e1156287. Epub 03 Mar 2016.

40. Pilon N, Raiwet D, Viger RS, Silversides DW. Novel pre- and post-gastrulation expression of Gata4 within cells of the inner cell mass and migratory neural crest cells. Dev Dyn. 2008;237(4):1133–43. 18351674.

41. Werner T, Hammer A, Wahlbuhl M, Bosl MR, Wegner M. Multiple conserved regulatory elements with overlapping functions determine Sox10 expression in mouse embryogenesis. Nucleic Acids Res. 2007;35(19):6526–38. 17897962.

42. Zhu L, Lee HO, Jordan CS, Cantrell VA, Southard-Smith EM, Shin MK. Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest-derived enteric neuron precursors. Nat Genet. 2004;36(7):732–7. Epub 2004/06/01. doi: 10.1038/ng1371 ng1371 [pii]. 15170213.

43. Kothary R, Clapoff S, Darling S, Perry MD, Moran LA, Rossant J. Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice. Development. 1989;105(4):707–14. Epub 1989/04/01. 2557196.

44. Vakilian H, Mirzaei M, Sharifi Tabar M, Pooyan P, Habibi Rezaee L, Parker L, et al. DDX3Y, a Male-Specific Region of Y Chromosome Gene, May Modulate Neuronal Differentiation. Journal of proteome research. 2015;14(9):3474–83. Epub 2015/07/07. doi: 10.1021/acs.jproteome.5b00512 26144214.

45. Poulat F, Girard F, Chevron MP, Goze C, Rebillard X, Calas B, et al. Nuclear localization of the testis determining gene product SRY. The Journal of cell biology. 1995;128(5):737–48. Epub 1995/03/01. doi: 10.1083/jcb.128.5.737 7876301; PubMed Central PMCID: PMC2120386.

46. van de Werken HJG, de Vree PJP, Splinter E, Holwerda SJB, Klous P, de Wit E, et al. Chapter four - 4C technology: Protocols and data analysis. In: Wu C, Allis CD, editors. Methods in Enzymology: Nucleosomes, Histones & Chromatin Part B. 513. USA, UK & The Netherlands: Academic Press; 2012. p. 89–112.

47. Cai M, Gao F, Lu W, Wang K. w4CSeq: software and web application to analyze 4C-seq data. Bioinformatics 2016;32(21):3333–5. Epub 2016/07/04. doi: 10.1093/bioinformatics/btw408 27378289.

48. Shang X, Vasudevan SA, Yu Y, Ge N, Ludwig AD, Wesson CL, et al. Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma. Oncogene. 2010;29(35):4938–46. doi: 10.1038/onc.2010.244 20562916.

49. Lokareddy RK, Bhardwaj A, Cingolani G. Atomic structure of dual-specificity phosphatase 26, a novel p53 phosphatase. Biochemistry. 2013;52(5):938–48. doi: 10.1021/bi301476m

50. Shi Y, Ma IT, Patel RH, Shang X, Chen Z, Zhao Y, et al. NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis. Cell Death Dis. 2015;6:e1841. Epub 2015/08/08. doi: 10.1038/cddis.2015.207 26247726; PubMed Central PMCID: PMC4558500.

51. Wu DW, Liu WS, Wang J, Chen CY, Cheng YW, Lee H. Reduced p21(WAF1/CIP1) via alteration of p53-DDX3 pathway is associated with poor relapse-free survival in early-stage human papillomavirus-associated lung cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 2011;17(7):1895–905. doi: 10.1158/1078-0432.CCR-10-2316 21325288.

52. Wu DW, Lee MC, Wang J, Chen CY, Cheng YW, Lee H. DDX3 loss by p53 inactivation promotes tumor malignancy via the MDM2/Slug/E-cadherin pathway and poor patient outcome in non-small-cell lung cancer. Oncogene. 2014;33(12):1515–26. doi: 10.1038/onc.2013.107 23584477.

53. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997;88(3):323–31. Epub 1997/02/07. doi: 10.1016/s0092-8674(00)81871-1 9039259.

54. Brooks CL, Gu W. Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation. Curr Opin Cell Biol. 2003;15(2):164–71. Epub 2003/03/22. doi: 10.1016/s0955-0674(03)00003-6 12648672.

55. Mendrysa SM, Perry ME. The p53 tumor suppressor protein does not regulate expression of its own inhibitor, MDM2, except under conditions of stress. Mol Cell Biol. 2000;20(6):2023–30. Epub 2000/02/25. doi: 10.1128/mcb.20.6.2023–2030.2000 10688649; PubMed Central PMCID: PMC110819.

56. Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med. 2008;14(2):125–33. Epub 2008/02/05. nm1725 [pii] doi: 10.1038/nm1725 18246078; PubMed Central PMCID: PMC3093709.

57. Kido T, Sun Z, Lau YC. Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice. Scientific reports. 2017;7(1):4113. Epub 2017/06/25. doi: 10.1038/s41598-017-04117-6 28646221; PubMed Central PMCID: PMC5482865.

58. Santos SF, de Oliveira HL, Yamada ES, Neves BC, Pereira A Jr. The Gut and Parkinson's Disease-A Bidirectional Pathway. Front Neurol. 2019;10:574. Epub 2019/06/20. doi: 10.3389/fneur.2019.00574 31214110; PubMed Central PMCID: PMC6558190.

59. Czech DP, Lee J, Sim H, Parish CL, Vilain E, Harley VR. The human testis-determining factor SRY localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism. J Neurochem. 2012;122(2):260–71. Epub 2012/05/10. doi: 10.1111/j.1471-4159.2012.07782.x 22568433; PubMed Central PMCID: PMC3529967.

60. Ditton HJ, Zimmer J, Kamp C, Rajpert-De Meyts E, Vogt PH. The AZFa gene DBY (DDX3Y) is widely transcribed but the protein is limited to the male germ cells by translation control. Hum Mol Genet. 2004;13(19):2333–41. Epub 2004/08/06. doi: 10.1093/hmg/ddh240 15294876.

61. Rosinski KV, Fujii N, Mito JK, Koo KK, Xuereb SM, Sala-Torra O, et al. DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells. Blood. 2008;111(9):4817–26. Epub 2008/02/27. doi: 10.1182/blood-2007-06-096313 18299450; PubMed Central PMCID: PMC2343610.

62. Wang T, Birsoy K, Hughes NW, Krupczak KM, Post Y, Wei JJ, et al. Identification and characterization of essential genes in the human genome. Science. 2015;350(6264):1096–101. Epub 2015/10/17. doi: 10.1126/science.aac7041 26472758; PubMed Central PMCID: PMC4662922.

63. Fuller-Pace FV. DEAD box RNA helicase functions in cancer. RNA biology. 2013;10(1):121–32. Epub 2013/01/29. doi: 10.4161/rna.23312 23353573; PubMed Central PMCID: PMC3590229.

64. He Y, Zhang D, Yang Y, Wang X, Zhao X, Zhang P, et al. A double-edged function of DDX3, as an oncogene or tumor suppressor, in cancer progression (Review). Oncol Rep. 2018;39(3):883–92. Epub 2018/01/13. doi: 10.3892/or.2018.6203 29328432.

65. Sekiguchi T, Iida H, Fukumura J, Nishimoto T. Human DDX3Y, the Y-encoded isoform of RNA helicase DDX3, rescues a hamster temperature-sensitive ET24 mutant cell line with a DDX3X mutation. Experimental cell research. 2004;300(1):213–22. Epub 2004/09/24. doi: 10.1016/j.yexcr.2004.07.005 15383328.

66. Szappanos D, Tschismarov R, Perlot T, Westermayer S, Fischer K, Platanitis E, et al. The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity. PLoS Pathog. 2018;14(11):e1007397. Epub 2018/11/27. doi: 10.1371/journal.ppat.1007397 30475900; PubMed Central PMCID: PMC6283616.

67. Foresta C, Ferlin A, Moro E. Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility. Hum Mol Genet. 2000;9(8):1161–9. Epub 2000/04/18. doi: 10.1093/hmg/9.8.1161 10767340.

68. Deng X, Berletch JB, Nguyen DK, Disteche CM. X chromosome regulation: diverse patterns in development, tissues and disease. Nat Rev Genet. 2014;15(6):367–78. doi: 10.1038/nrg3687 24733023.

69. Geissler R, Golbik RP, Behrens SE. The DEAD-box helicase DDX3 supports the assembly of functional 80S ribosomes. Nucleic Acids Res. 2012;40(11):4998–5011. Epub 2012/02/11. doi: 10.1093/nar/gks070 22323517; PubMed Central PMCID: PMC3367175.

70. Mazeyrat S, Saut N, Grigoriev V, Mahadevaiah SK, Ojarikre OA, Rattigan A, et al. A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis. Nat Genet. 2001;29(1):49–53. Epub 2001/08/31. doi: 10.1038/ng717 11528390.

71. Kastenhuber ER, Lowe SW. Putting p53 in Context. Cell. 2017;170(6):1062–78. Epub 2017/09/09. doi: 10.1016/j.cell.2017.08.028 28886379; PubMed Central PMCID: PMC5743327.

72. Bowen ME, McClendon J, Long HK, Sorayya A, Van Nostrand JL, Wysocka J, et al. The Spatiotemporal Pattern and Intensity of p53 Activation Dictates Phenotypic Diversity in p53-Driven Developmental Syndromes. Dev Cell. 2019;50(2):212–28 e6. Epub 2019/06/11. doi: 10.1016/j.devcel.2019.05.015 31178404; PubMed Central PMCID: PMC6650355.

73. Calo E, Gu B, Bowen ME, Aryan F, Zalc A, Liang J, et al. Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders. Nature. 2018;554(7690):112–7. doi: 10.1038/nature25449 29364875; PubMed Central PMCID: PMC5927778.

74. Konstantinidou C, Taraviras S, Pachnis V. Geminin prevents DNA damage in vagal neural crest cells to ensure normal enteric neurogenesis. BMC biology. 2016;14(1):94. Epub 2016/10/26. doi: 10.1186/s12915-016-0314-x 27776507; PubMed Central PMCID: PMC5075986.

75. Fattahi F, Steinbeck JA, Kriks S, Tchieu J, Zimmer B, Kishinevsky S, et al. Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease. Nature. 2016. doi: 10.1038/nature16951 26863197.

76. Lai FP, Lau ST, Wong JK, Gui H, Wang RX, Zhou T, et al. Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells Via Clustered Regularly Interspaced Short Palindromic Repeats/Cas9, Restores Neural Crest Cell Function. Gastroenterology. 2017;153(1):139–53 e8. Epub 2017/03/28. doi: 10.1053/j.gastro.2017.03.014 28342760.

77. Heuckeroth RO, Schafer KH. Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention. Dev Biol. 2016;417(2):188–97. doi: 10.1016/j.ydbio.2016.03.017 26997034; PubMed Central PMCID: PMC5026873.

78. Sakai D, Dixon J, Achilleos A, Dixon M, Trainor PA. Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation. Nature communications. 2016;7:10328. Epub 2016/01/23. doi: 10.1038/ncomms10328 26792133; PubMed Central PMCID: PMC4735750.

79. Nagy A, Gertsenstein M, Vintersten K, Behringer R. Manipulating the mouse embryo, A laboratory manual, 3rd Edition. Cold spring Harbor, New-York: Cold Spring Harbor Laboratory Press; 2003.

80. Methot D, Reudelhuber TL, Silversides DW. Evaluation of tyrosinase minigene co-injection as a marker for genetic manipulations in transgenic mice. Nucleic Acids Res. 1995;23(22):4551–6. 8524641.

81. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819–23. Epub 2013/01/03. doi: 10.1126/science.1231143 23287718.

82. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell. 2013;153(4):910–8. https://doi.org/10.1016/j.cell.2013.04.025.

83. Belanger C, Berube-Simard FA, Leduc E, Bernas G, Campeau PM, Lalani SR, et al. Dysregulation of cotranscriptional alternative splicing underlies CHARGE syndrome. Proc Natl Acad Sci U S A. 2018;115(4):E620–E9. doi: 10.1073/pnas.1715378115 29311329; PubMed Central PMCID: PMC5789929.

84. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402–8. https://doi.org/10.1006/meth.2001.1262.

85. Liu L, Shi G, Thirumalai D, Hyeon C. Chain organization of human interphase chromosome determines the spatiotemporal dynamics of chromatin loci. PLoS Computational Biology. 2018;14(12):e1006617. doi: 10.1371/journal.pcbi.1006617

86. Du Z, Zheng H, Huang B, Ma R, Wu J, Zhang X, et al. Allelic reprogramming of 3D chromatin architecture during early mammalian development. Nature. 2017;547(7662):232–5. Epub 2017/07/14. doi: 10.1038/nature23263 28703188.

87. Ke Y, Xu Y, Chen X, Feng S, Liu Z, Sun Y, et al. 3D Chromatin Structures of Mature Gametes and Structural Reprogramming during Mammalian Embryogenesis. Cell. 2017;170(2):367–81 e20. Epub 2017/07/15. doi: 10.1016/j.cell.2017.06.029 28709003.

88. Enomoto H, Araki T, Jackman A, Heuckeroth RO, Snider WD, Johnson EM Jr., et al. GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron. 1998;21(2):317–24. 9728913.

89. Sanchez-Ferras O, Coutaud B, Djavanbakht Samani T, Tremblay I, Souchkova O, Pilon N. Caudal-related homeobox (Cdx) protein-dependent integration of canonical Wnt signaling on paired-box 3 (Pax3) neural crest enhancer. J Biol Chem. 2012;287(20):16623–35. Epub 2012/03/30. M112.356394 [pii] doi: 10.1074/jbc.M112.356394 22457346; PubMed Central PMCID: PMC3351347.

90. Silversides DW, Raiwet DL, Souchkova O, Viger RS, Pilon N. Transgenic mouse analysis of Sry expression during the pre- and peri-implantation stage. Dev Dyn. 2012;241(7):1192–204. Epub 2012/04/28. doi: 10.1002/dvdy.23798 22539273.


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 9
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Současné pohledy na riziko v parodontologii
nový kurz
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Aktuální možnosti diagnostiky a léčby litiáz
Autoři: MUDr. Tomáš Ürge, PhD.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se