NCK-associated protein 1 like (nckap1l) minor splice variant regulates intrahepatic biliary network morphogenesis
Autoři:
Kimia Ghaffari aff001; Lain X. Pierce aff001; Maria Roufaeil aff001; Isabel Gibson aff001; Kevin Tae aff001; Saswat Sahoo aff001; James R. Cantrell aff001; Olov Andersson aff003; Jasmine Lau aff001; Takuya F. Sakaguchi aff001
Působiště autorů:
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
aff001; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States of America
aff002; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
aff003; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States of America
aff004
Vyšlo v časopise:
NCK-associated protein 1 like (nckap1l) minor splice variant regulates intrahepatic biliary network morphogenesis. PLoS Genet 17(3): e1009402. doi:10.1371/journal.pgen.1009402
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009402
Souhrn
Impaired formation of the intrahepatic biliary network leads to cholestatic liver diseases, which are frequently associated with autoimmune disorders. Using a chemical mutagenesis strategy in zebrafish combined with computational network analysis, we screened for novel genes involved in intrahepatic biliary network formation. We positionally cloned a mutation in the nckap1l gene, which encodes a cytoplasmic adaptor protein for the WAVE regulatory complex. The mutation is located in the last exon after the stop codon of the primary splice isoform, only disrupting a previously unannotated minor splice isoform, which indicates that the minor splice isoform is responsible for the intrahepatic biliary network phenotype. CRISPR/Cas9-mediated nckap1l deletion, which disrupts both the primary and minor isoforms, showed the same defects. In the liver of nckap1l mutant larvae, WAVE regulatory complex component proteins are degraded specifically in biliary epithelial cells, which line the intrahepatic biliary network, thus disrupting the actin organization of these cells. We further show that nckap1l genetically interacts with the Cdk5 pathway in biliary epithelial cells. These data together indicate that although nckap1l was previously considered to be a hematopoietic cell lineage-specific protein, its minor splice isoform acts in biliary epithelial cells to regulate intrahepatic biliary network formation.
Klíčová slova:
Actins – Epithelial cells – Genetic networks – Heterozygosity – Larvae – Phenotypes – Zebrafish – Branching morphogenesis
Zdroje
1. Lee HC, Yeung CY, Chang PY, Sheu JC, Wang NL. Dilatation of the biliary tree in children: sonographic diagnosis and its clinical significance. Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine. 2000;19(3):177–82; quiz 83–4. Epub 2000/03/10. doi: 10.7863/jum.2000.19.3.177 10709833.
2. Mack CL, Sokol RJ. Unraveling the pathogenesis and etiology of biliary atresia. Pediatric research. 2005;57(5 Pt 2):87R–94R. Epub 2005/04/09. doi: 10.1203/01.PDR.0000159569.57354.47 15817506.
3. Sokol RJ, Mack C, Narkewicz MR, Karrer FM. Pathogenesis and outcome of biliary atresia: current concepts. Journal of pediatric gastroenterology and nutrition. 2003;37(1):4–21. Epub 2003/06/27. doi: 10.1097/00005176-200307000-00003 12827000.
4. Garcia-Barcelo MM, Yeung MY, Miao XP, Tang CS, Cheng G, So MT, et al. Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2. Human molecular genetics. 2010;19(14):2917–25. Epub 2010/05/13. doi: 10.1093/hmg/ddq196 20460270; PubMed Central PMCID: PMC2893814.
5. Tsai EA, Grochowski CM, Loomes KM, Bessho K, Hakonarson H, Bezerra JA, et al. Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia. Human genetics. 2014;133(2):235–43. Epub 2013/10/10. doi: 10.1007/s00439-013-1368-2 24104524; PubMed Central PMCID: PMC3901047.
6. Tang V, Cofer ZC, Cui S, Sapp V, Loomes KM, Matthews RP. Loss of a Candidate Biliary Atresia Susceptibility Gene, add3a, Causes Biliary Developmental Defects in Zebrafish. Journal of pediatric gastroenterology and nutrition. 2016;63(5):524–30. doi: 10.1097/MPG.0000000000001375 27526058; PubMed Central PMCID: PMC5074882.
7. Hartley JL, Davenport M, Kelly DA. Biliary atresia. Lancet. 2009;374(9702):1704–13. doi: 10.1016/S0140-6736(09)60946-6 19914515.
8. Dimri M, Bilogan C, Pierce LX, Naegele G, Vasanji A, Gibson I, et al. Three-dimensional structural analysis reveals a Cdk5-mediated kinase cascade regulating hepatic biliary network branching in zebrafish. Development. 2017;144(14):2595–605. doi: 10.1242/dev.147397 28720653; PubMed Central PMCID: PMC5536925.
9. Goley ED, Welch MD. The ARP2/3 complex: an actin nucleator comes of age. Nat Rev Mol Cell Biol. 2006;7(10):713–26. doi: 10.1038/nrm2026 16990851.
10. Takenawa T, Suetsugu S. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol. 2007;8(1):37–48. doi: 10.1038/nrm2069 17183359.
11. Kurisu S, Takenawa T. The WASP and WAVE family proteins. Genome Biol. 2009;10(6):226. doi: 10.1186/gb-2009-10-6-226 19589182; PubMed Central PMCID: PMC2718491.
12. Kunda P, Craig G, Dominguez V, Baum B. Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE to regulate the formation of actin-based protrusions. Curr Biol. 2003;13(21):1867–75. Epub 2003/11/01. doi: 10.1016/j.cub.2003.10.005 14588242.
13. Soto MC, Qadota H, Kasuya K, Inoue M, Tsuboi D, Mello CC, et al. The GEX-2 and GEX-3 proteins are required for tissue morphogenesis and cell migrations in C. elegans. Genes Dev. 2002;16(5):620–32. Epub 2002/03/06. doi: 10.1101/gad.955702 11877381; PubMed Central PMCID: PMC155352.
14. Ibarra N, Blagg SL, Vazquez F, Insall RH. Nap1 regulates Dictyostelium cell motility and adhesion through SCAR-dependent and -independent pathways. Curr Biol. 2006;16(7):717–22. Epub 2006/04/04. doi: 10.1016/j.cub.2006.02.068 16581519.
15. Kim Y, Sung JY, Ceglia I, Lee KW, Ahn JH, Halford JM, et al. Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology. Nature. 2006;442(7104):814–7. doi: 10.1038/nature04976 WOS:000239792700046. 16862120
16. Park H, Staehling-Hampton K, Appleby MW, Brunkow ME, Habib T, Zhang Y, et al. A point mutation in the murine Hem1 gene reveals an essential role for Hematopoietic protein 1 in lymphopoiesis and innate immunity. J Exp Med. 2008;205(12):2899–913. doi: 10.1084/jem.20080340 19015308; PubMed Central PMCID: PMC2585840.
17. Sparks EE, Huppert KA, Brown MA, Washington MK, Huppert SS. Notch signaling regulates formation of the three-dimensional architecture of intrahepatic bile ducts in mice. Hepatology. 2010;51(4):1391–400. doi: 10.1002/hep.23431 20069650; PubMed Central PMCID: PMC2995854.
18. Weiner OD, Rentel MC, Ott A, Brown GE, Jedrychowski M, Yaffe MB, et al. Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis. PLoS Biol. 2006;4(2):e38. doi: 10.1371/journal.pbio.0040038 16417406; PubMed Central PMCID: PMC1334198.
19. Baralle FE, Giudice J. Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol. 2017;18(7):437–51. doi: 10.1038/nrm.2017.27 28488700.
20. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, et al. Alternative isoform regulation in human tissue transcriptomes. Nature. 2008;456(7221):470–6. doi: 10.1038/nature07509 18978772; PubMed Central PMCID: PMC2593745.
21. Lorent K, Moore JC, Siekmann AF, Lawson N, Pack M. Reiterative Use of the Notch Signal During Zebrafish Intrahepatic Biliary Development. Dev Dynam. 2010;239(3):855–64. doi: 10.1002/dvdy.22220 ISI:000275633100012. 20108354
22. Parsons MJ, Pisharath H, Yusuff S, Moore JC, Siekmann AF, Lawson N, et al. Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas. Mech Dev. 2009;126(10):898–912. doi: 10.1016/j.mod.2009.07.002 19595765; PubMed Central PMCID: PMC3640481.
23. Parichy DM, Elizondo MR, Mills MG, Gordon TN, Engeszer RE. Normal table of postembryonic zebrafish development: staging by externally visible anatomy of the living fish. Dev Dyn. 2009;238(12):2975–3015. Epub 2009/11/06. doi: 10.1002/dvdy.22113 19891001; PubMed Central PMCID: PMC3030279.
24. Hill JT, Demarest BL, Bisgrove BW, Gorsi B, Su YC, Yost HJ. MMAPPR: mutation mapping analysis pipeline for pooled RNA-seq. Genome Res. 2013;23(4):687–97. doi: 10.1101/gr.146936.112 23299975; PubMed Central PMCID: PMC3613585.
25. Miller AC, Obholzer ND, Shah AN, Megason SG, Moens CB. RNA-seq-based mapping and candidate identification of mutations from forward genetic screens. Genome Res. 2013;23(4):679–86. doi: 10.1101/gr.147322.112 23299976; PubMed Central PMCID: PMC3613584.
26. Leshchiner I, Alexa K, Kelsey P, Adzhubei I, Austin-Tse CA, Cooney JD, et al. Mutation mapping and identification by whole-genome sequencing. Genome Res. 2012;22(8):1541–8. doi: 10.1101/gr.135541.111 22555591; PubMed Central PMCID: PMC3409267.
27. Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562–78. doi: 10.1038/nprot.2012.016 22383036; PubMed Central PMCID: PMC3334321.
28. 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. doi: 10.1126/science.1231143 23287718; PubMed Central PMCID: PMC3795411.
29. Hoshijima K, Jurynec MJ, Klatt Shaw D, Jacobi AM, Behlke MA, Grunwald DJ. Highly Efficient CRISPR-Cas9-Based Methods for Generating Deletion Mutations and F0 Embryos that Lack Gene Function in Zebrafish. Dev Cell. 2019;51(5):645–57 e4. doi: 10.1016/j.devcel.2019.10.004 31708433; PubMed Central PMCID: PMC6891219.
30. Farber SA, Pack M, Ho SY, Johnson ID, Wagner DS, Dosch R, et al. Genetic analysis of digestive physiology using fluorescent phospholipid reporters. Science. 2001;292(5520):1385–8. Epub 2001/05/19. doi: 10.1126/science.1060418 11359013.
31. Blagg SL, Stewart M, Sambles C, Insall RH. PIR121 regulates pseudopod dynamics and SCAR activity in Dictyostelium. Curr Biol. 2003;13(17):1480–7. doi: 10.1016/s0960-9822(03)00580-3 WOS:000185171300017. 12956949
32. Zhu ZR, Bhat KM. The Hem protein mediates neuronal migration by inhibiting WAVE degradation and functions opposite of Abelson tyrosine kinase. Dev Biol. 2011;357(2):283–94. doi: 10.1016/j.ydbio.2011.06.025 WOS:000294834400001. 21726548
33. Schenck A, Qurashi A, Carrera P, Bardoni B, Diebold C, Schejter E, et al. WAVE/SCAR, a multifunctional complex coordinating different aspects of neuronal connectivity. Dev Biol. 2004;274(2):260–70. doi: 10.1016/j.ydbio.2004.07.009 15385157.
34. Echarri A, Lai MJ, Robinson MR, Pendergast AM. Abl interactor 1 (Abi-1) wave-binding and SNARE domains regulate its nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels. Mol Cell Biol. 2004;24(11):4979–93. Epub 2004/05/15. doi: 10.1128/MCB.24.11.4979-4993.2004 15143189; PubMed Central PMCID: PMC416433.
35. Liu KC, Leuckx G, Sakano D, Seymour PA, Mattsson CL, Rautio L, et al. Inhibition of Cdk5 Promotes beta-Cell Differentiation From Ductal Progenitors. Diabetes. 2018;67(1):58–70. doi: 10.2337/db16-1587 28986398; PubMed Central PMCID: PMC6463766.
36. Park H, Chan MM, Iritani BM. Hem-1: putting the "WAVE" into actin polymerization during an immune response. FEBS Lett. 2010;584(24):4923–32. doi: 10.1016/j.febslet.2010.10.018 20969869; PubMed Central PMCID: PMC3363972.
37. Nussbaum JM, Liu LJ, Hasan SA, Schaub M, McClendon A, Stainier DY, et al. Homeostatic generation of reactive oxygen species protects the zebrafish liver from steatosis. Hepatology. 2013;58(4):1326–38. Epub 2013/06/08. doi: 10.1002/hep.26551 23744565; PubMed Central PMCID: PMC3791216.
38. Schaub M, Nussbaum J, Verkade H, Ober EA, Stainier DY, Sakaguchi TF. Mutation of zebrafish Snapc4 is associated with loss of the intrahepatic biliary network. Dev Biol. 2012;363(1):128–37. Epub 2012/01/10. S0012-1606(11)01445-X [pii] 10.1016/j.ydbio.2011.12.025. doi: 10.1016/j.ydbio.2011.12.025 22222761.
39. Villasenor A, Gauvrit S, Collins MM, Maischein HM, Stainier DYR. Hhex regulates the specification and growth of the hepatopancreatic ductal system. Dev Biol 2020;458(2):228–36. Epub 2019/11/08. doi: 10.1016/j.ydbio.2019.10.021 31697936
40. Thestrup MI, Caviglia S, Cayuso J, Heyne RLS, Ahmad R, Hofmeister W, et al. A morphogenetic EphB/EphrinB code controls hepatopancreatic duct formation. Nat Commun. 2019;10(1):5220. Epub 2019/11/21. doi: 10.1038/s41467-019-13149-7 31745086; PubMed Central PMCID: PMC6864101.
41. Parsons MJ, Pisharath H, Yusuff S, Moore JC, Siekmann AF, Lawson N, et al. Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas. Mech Develop. 2009;126(10):898–912. doi: 10.1016/j.mod.2009.07.002 ISI:000271237000013. 19595765
42. Matthews RP, Lorent K, Russo P, Pack M. The zebrafish onecut gene hnf-6 functions in an evolutionarily conserved genetic pathway that regulates vertebrate biliary development. Dev Biol. 2004;274(2):245–59. doi: 10.1016/j.ydbio.2004.06.016 15385156.
43. Matthews RP, Eauclaire SF, Mugnier M, Lorent K, Cui S, Ross MM, et al. DNA hypomethylation causes bile duct defects in zebrafish and is a distinguishing feature of infantile biliary atresia. Hepatology. 2011;53(3):905–14. Epub 2011/02/15. doi: 10.1002/hep.24106 21319190; PubMed Central PMCID: PMC3075951.
44. Gao C, Huang W, Gao Y, Lo LJ, Luo L, Huang H, et al. Zebrafish hhex-null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1. J Mol Cell Biol. 2019;11(6):448–62. Epub 2018/11/15. doi: 10.1093/jmcb/mjy068 30428031; PubMed Central PMCID: PMC6604603.
45. Manfroid I, Ghaye A, Naye F, Detry N, Palm S, Pan L, et al. Zebrafish sox9b is crucial for hepatopancreatic duct development and pancreatic endocrine cell regeneration. Dev Biol. 2012;366(2):268–78. Epub 2012/04/28. doi: 10.1016/j.ydbio.2012.04.002 22537488; PubMed Central PMCID: PMC3364407.
46. Delous M, Yin C, Shin D, Ninov N, Debrito Carten J, Pan L, et al. Sox9b is a key regulator of pancreaticobiliary ductal system development. PLoS Genet. 2012;8(6):e1002754. Epub 2012/06/22. doi: 10.1371/journal.pgen.1002754 22719264; PubMed Central PMCID: PMC3375260.
47. Dong PD, Munson CA, Norton W, Crosnier C, Pan X, Gong Z, et al. Fgf10 regulates hepatopancreatic ductal system patterning and differentiation. Nat Genet. 2007;39(3):397–402. Epub 2007/01/30. doi: 10.1038/ng1961 17259985.
48. Ober EA, Lemaigre FP. Development of the liver: Insights into organ and tissue morphogenesis. J Hepatol. 2018;68(5):1049–62. Epub 2018/01/18. doi: 10.1016/j.jhep.2018.01.005 29339113.
49. Hall C, Flores MV, Storm T, Crosier K, Crosier P. The zebrafish lysozyme C promoter drives myeloid-specific expression in transgenic fish. BMC Dev Biol. 2007;7:42. Epub 2007/05/05. doi: 10.1186/1471-213X-7-42 17477879; PubMed Central PMCID: PMC1877083.
50. Jin SW, Beis D, Mitchell T, Chen JN, Stainier DY. Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development. 2005;132(23):5199–209. Epub 2005/10/28. doi: 10.1242/dev.02087 16251212.
51. Fujita M, Cha YR, Pham VN, Sakurai A, Roman BL, Gutkind JS, et al. Assembly and patterning of the vascular network of the vertebrate hindbrain. Development. 2011;138(9):1705–15. Epub 2011/03/25. doi: 10.1242/dev.058776 21429985. PubMed Central PMCID: PMC3074447.
52. Driever W, Solnica-Krezel L, Schier AF, Neuhauss SC, Malicki J, Stemple DL, et al. A genetic screen for mutations affecting embryogenesis in zebrafish. Development. 1996;123:37–46. 9007227.
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