Deregulation of the Protocadherin Gene Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy

English version České info

Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts. Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains, altering the shape of selective groups of muscles in the shoulder and face. These shape abnormalities were followed by early onset regionalised muscle defects in adult Fat1-deficient mice. Tissue-specific ablation of Fat1 driven by Pax3-cre reproduced muscle shape defects in limb but not face muscles, indicating a cell-autonomous contribution of Fat1 in migrating muscle precursors. Strikingly, the topography of muscle abnormalities caused by Fat1 loss-of-function resembles that of human patients with facioscapulohumeral dystrophy (FSHD). FAT1 lies near the critical locus involved in causing FSHD, and Fat1 mutant mice also show retinal vasculopathy, mimicking another symptom of FSHD, and showed abnormal inner ear patterning, predictive of deafness, reminiscent of another burden of FSHD. Muscle-specific reduction of FAT1 expression and promoter silencing was observed in foetal FSHD1 cases. CGH array-based studies identified deletion polymorphisms within a putative regulatory enhancer of FAT1, predictive of tissue-specific depletion of FAT1 expression, which preferentially segregate with FSHD. Our study identifies FAT1 as a critical determinant of muscle form, misregulation of which associates with FSHD.

Vyšlo v časopise: Deregulation of the Protocadherin Gene Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy. PLoS Genet 9(6): e32767. doi:10.1371/journal.pgen.1003550
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003550

Souhrn

Zdroje

1. ShiX, GarryDJ (2006) Muscle stem cells in development, regeneration, and disease. Genes Dev 20: 1692–1708.

2. SambasivanR, Gayraud-MorelB, DumasG, CimperC, PaisantS, et al. (2009) Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates. Dev Cell 16: 810–821.

3. ShihHP, GrossMK, KioussiC (2008) Muscle development: forming the head and trunk muscles. Acta Histochem 110: 97–108.

4. LisiMT, CohnRD (2007) Congenital muscular dystrophies: new aspects of an expanding group of disorders. Biochim Biophys Acta 1772: 159–172.

5. EmeryAE (2002) The muscular dystrophies. Lancet 359: 687–695.

6. TawilR, Van Der MaarelSM (2006) Facioscapulohumeral muscular dystrophy. Muscle Nerve 34: 1–15.

7. OttavianiA, GilsonE, MagdinierF (2008) Telomeric position effect: from the yeast paradigm to human pathologies? Biochimie 90: 93–107.

8. OttavianiA, Rival-GervierS, BoussouarA, FoersterAM, RondierD, et al. (2009) The D4Z4 macrosatellite repeat acts as a CTCF and A-type lamins-dependent insulator in facio-scapulo-humeral dystrophy. PLoS Genet 5: e1000394.

9. MasnyPS, ChanOY, de GreefJC, BengtssonU, EhrlichM, et al. (2009) Analysis of allele-specific RNA transcription in FSHD by RNA-DNA FISH in single myonuclei. Eur J Hum Genet 18(4): 448–56.

10. WinokurST, ChenYW, MasnyPS, MartinJH, EhmsenJT, et al. (2003) Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation. Hum Mol Genet 12: 2895–2907.

11. GabelliniD, GreenMR, TuplerR (2002) Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Cell 110: 339–348.

12. GabelliniD, D'AntonaG, MoggioM, PrelleA, ZeccaC, et al. (2006) Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1. Nature 439: 973–977.

13. XuX, TsumagariK, SowdenJ, TawilR, BoyleAP, et al. (2009) DNaseI hypersensitivity at gene-poor, FSH dystrophy-linked 4q35.2. Nucleic Acids Res 37: 7381–7393.

14. SniderL, GengLN, LemmersRJ, KybaM, WareCB, et al. (2010) Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene. PLoS Genet 6: e1001181.

15. DmitrievP, LipinskiM, VassetzkyYS (2009) Pearls in the junk: dissecting the molecular pathogenesis of facioscapulohumeral muscular dystrophy. Neuromuscul Disord 19: 17–20.

16. van der MaarelSM, TawilR, TapscottSJ (2011) Facioscapulohumeral muscular dystrophy and DUX4: breaking the silence. Trends Mol Med 17: 252–258.

17. LemmersRJLF, Van der VlietPJ, KloosterR, SacconiS, CamañoP, et al. (2010) A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy. Science 329(5999): 1650–1653.

18. GengLN, YaoZ, SniderL, FongAP, CechJN, et al. (2012) DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy. Dev Cell 22: 38–51.

19. WallaceLM, GarwickSE, MeiW, BelayewA, CoppeeF, et al. (2011) DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo. Ann Neurol 69: 540–552.

20. AnsseauE, Laoudj-ChenivesseD, MarcowyczA, TassinA, VanderplanckC, et al. (2009) DUX4c is up-regulated in FSHD. It induces the MYF5 protein and human myoblast proliferation. PLoS One 4: e7482.

21. DixitM, AnsseauE, TassinA, WinokurS, ShiR, et al. (2007) DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1. Proc Natl Acad Sci U S A 104: 18157–18162.

22. LemmersRJ, TawilR, PetekLM, BalogJ, BlockGJ, et al. (2012) Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat Genet (12): 1370–4.

23. BosnakovskiD, DaughtersRS, XuZ, SlackJM, KybaM (2009) Biphasic myopathic phenotype of mouse DUX, an ORF within conserved FSHD-related repeats. PLoS One 4: e7003.

24. BosnakovskiD, XuZ, GangEJ, GalindoCL, LiuM, et al. (2008) An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies. EMBO J 27: 2766–2779.

25. SopkoR, McNeillH (2009) The skinny on Fat: an enormous cadherin that regulates cell adhesion, tissue growth, and planar cell polarity. Curr Opin Cell Biol 21: 717–723.

26. SimonsM, MlodzikM (2008) Planar cell polarity signaling: from fly development to human disease. Annu Rev Genet 42: 517–540.

27. TanoueT, TakeichiM (2005) New insights into Fat cadherins. J Cell Sci 118: 2347–2353.

28. HarumotoT, ItoM, ShimadaY, KobayashiTJ, UedaHR, et al. (2010) Atypical Cadherins Dachsous and Fat Control Dynamics of Noncentrosomal Microtubules in Planar Cell Polarity. Dev Cell (3)389–401.

29. AigouyB, FarhadifarR, StapleDB, SagnerA, RoperJC, et al. (2010) Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell 142: 773–786.

30. Lopez-SchierH, StarrCJ, KapplerJA, KollmarR, HudspethAJ (2004) Directional cell migration establishes the axes of planar polarity in the posterior lateral-line organ of the zebrafish. Dev Cell 7: 401–412.

31. SmithTG, Van HaterenN, TickleC, WilsonSA (2007) The expression of Fat-1 cadherin during chick limb development. Int J Dev Biol 51: 173–176.

32. VasyutinaE, SteblerJ, Brand-SaberiB, SchulzS, RazE, et al. (2005) CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells. Genes Dev 19: 2187–2198.

33. PanteG, ThompsonJ, LamballeF, IwataT, FerbyI, et al. (2005) Mitogen-inducible gene 6 is an endogenous inhibitor of HGF/Met-induced cell migration and neurite growth. J Cell Biol 171: 337–348.

34. BarberTD, BarberMC, TomescuO, BarrFG, RubenS, et al. (2002) Identification of target genes regulated by PAX3 and PAX3-FKHR in embryogenesis and alveolar rhabdomyosarcoma. Genomics 79: 278–284.

35. HouR, LiuL, AneesS, HiroyasuS, SibingaNE (2006) The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals. J Cell Biol 173: 417–429.

36. CianiL, PatelA, AllenND, ffrench-ConstantC (2003) Mice lacking the giant protocadherin mFAT1 exhibit renal slit junction abnormalities and a partially penetrant cyclopia and anophthalmia phenotype. Mol Cell Biol 23: 3575–3582.

37. WeiCL, WuQ, VegaVB, ChiuKP, NgP, et al. (2006) A global map of p53 transcription-factor binding sites in the human genome. Cell 124: 207–219.

38. MeletisK, WirtaV, HedeSM, NisterM, LundebergJ, et al. (2006) p53 suppresses the self-renewal of adult neural stem cells. Development 133: 363–369.

39. PrunottoC, CrepaldiT, ForniPE, IeraciA, KellyRG, et al. (2004) Analysis of Mlc-lacZ Met mutants highlights the essential function of Met for migratory precursors of hypaxial muscles and reveals a role for Met in the development of hyoid arch-derived facial muscles. Dev Dyn 231: 582–591.

40. HaaseG, DessaudE, GarcesA, de BovisB, BirlingM, et al. (2002) GDNF acts through PEA3 to regulate cell body positioning and muscle innervation of specific motor neuron pools. Neuron 35: 893–905.

41. LeightonPA, MitchellKJ, GoodrichLV, LuX, PinsonK, et al. (2001) Defining brain wiring patterns and mechanisms through gene trapping in mice. Nature 410: 174–179.

42. MitchellKJ, PinsonKI, KellyOG, BrennanJ, ZupicichJ, et al. (2001) Functional analysis of secreted and transmembrane proteins critical to mouse development. Nat Genet 28: 241–249.

43. KellyRG, ZammitPS, SchneiderA, AlonsoS, BibenC, et al. (1997) Embryonic and fetal myogenic programs act through separate enhancers at the MLC1F/3F locus. Dev Biol 187: 183–199.

44. YamanakaK, ChunSJ, BoilleeS, Fujimori-TonouN, YamashitaH, et al. (2008) Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci 11: 251–253.

45. EnglekaKA, GitlerAD, ZhangM, ZhouDD, HighFA, et al. (2005) Insertion of Cre into the Pax3 locus creates a new allele of Splotch and identifies unexpected Pax3 derivatives. Dev Biol 280: 396–406.

46. TheisS, PatelK, ValasekP, OttoA, PuQ, et al. (2010) The occipital lateral plate mesoderm is a novel source for vertebrate neck musculature. Development 137: 2961–2971.

47. Franzini-ArmstrongC, JorgensenAO (1994) Structure and development of E-C coupling units in skeletal muscle. Annu Rev Physiol 56: 509–534.

48. BraunGS, KretzlerM, HeiderT, FloegeJ, HolzmanLB, et al. (2007) Differentially spliced isoforms of FAT1 are asymmetrically distributed within migrating cells. J Biol Chem 282: 22823–22833.

49. MaggT, SchreinerD, SolisGP, BadeEG, HoferHW (2005) Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus. Exp Cell Res 307: 100–108.

50. SadeqzadehE, de BockCE, ZhangXD, ShipmanKL, ScottNM, et al. (2011) Dual Processing of FAT1 Cadherin Protein by Human Melanoma Cells Generates Distinct Protein Products. J Biol Chem 286: 28181–28191.

51. SopkoR, SilvaE, ClaytonL, GardanoL, Barrios-RodilesM, et al. (2009) Phosphorylation of the tumor suppressor fat is regulated by its ligand Dachsous and the kinase discs overgrown. Curr Biol 19: 1112–1117.

52. FengY, IrvineKD (2009) Processing and phosphorylation of the Fat receptor. Proc Natl Acad Sci U S A 106: 11989–11994.

53. ReedP, PorterNC, StrongJ, PumplinDW, CorseAM, et al. (2006) Sarcolemmal reorganization in facioscapulohumeral muscular dystrophy. Ann Neurol 59: 289–297.

54. FitzsimonsRB, GurwinEB, BirdAC (1987) Retinal vascular abnormalities in facioscapulohumeral muscular dystrophy. A general association with genetic and therapeutic implications. Brain 110(Pt 3): 631–648.

55. GurwinEB, FitzsimonsRB, SehmiKS, BirdAC (1985) Retinal telangiectasis in facioscapulohumeral muscular dystrophy with deafness. Arch Ophthalmol 103: 1695–1700.

56. SaburiS, HesterI, GoodrichL, McNeillH (2012) Functional interactions between Fat family cadherins in tissue morphogenesis and planar polarity. Development 139: 1806–1820.

57. SaburiS, HesterI, FischerE, PontoglioM, EreminaV, et al. (2008) Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nat Genet 40: 1010–1015.

58. GoodrichLV (2008) The plane facts of PCP in the CNS. Neuron 60: 9–16.

59. KellyR, AlonsoS, TajbakhshS, CossuG, BuckinghamM (1995) Myosin light chain 3F regulatory sequences confer regionalized cardiac and skeletal muscle expression in transgenic mice. J Cell Biol 129: 383–396.

60. TsumagariK, ChangSC, LaceyM, BaribaultC, ChitturSV, et al. (2011) Gene expression during normal and FSHD myogenesis. BMC Med Genomics 4: 67.

61. HeintzmanND, StuartRK, HonG, FuY, ChingCW, et al. (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39: 311–318.

62. CaoR, WangL, WangH, XiaL, Erdjument-BromageH, et al. (2002) Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298: 1039–1043.

63. de GreefJC, LemmersRJ, CamanoP, DayJW, SacconiS, et al. (2010) Clinical features of facioscapulohumeral muscular dystrophy 2. Neurology 75: 1548–1554.

64. de GreefJC, LemmersRJ, van EngelenBG, SacconiS, VenanceSL, et al. (2009) Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Hum Mutat 30: 1449–1459.

65. BarrettMT, SchefferA, Ben-DorA, SampasN, LipsonD, et al. (2004) Comparative genomic hybridization using oligonucleotide microarrays and total genomic DNA. Proc Natl Acad Sci U S A 101: 17765–17770.

66. CelnikerSE, DillonLA, GersteinMB, GunsalusKC, HenikoffS, et al. (2009) Unlocking the secrets of the genome. Nature 459: 927–930.

67. ErnstJ, KheradpourP, MikkelsenTS, ShoreshN, WardLD, et al. (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473: 43–49.

68. MatsuzakiH, WangPH, HuJ, RavaR, FuGK (2009) High resolution discovery and confirmation of copy number variants in 90 Yoruba Nigerians. Genome Biol 10: R125.

69. BastockR, StruttD (2007) The planar polarity pathway promotes coordinated cell migration during Drosophila oogenesis. Development 134: 3055–3064.

70. NathanE, MonovichA, Tirosh-FinkelL, HarrelsonZ, RoussoT, et al. (2008) The contribution of Islet1-expressing splanchnic mesoderm cells to distinct branchiomeric muscles reveals significant heterogeneity in head muscle development. Development 135: 647–657.

71. LescroartF, KellyRG, Le GarrecJF, NicolasJF, MeilhacSM, et al. (2010) Clonal analysis reveals common lineage relationships between head muscles and second heart field derivatives in the mouse embryo. Development 137: 3269–3279.

72. NodenDM, Francis-WestP (2006) The differentiation and morphogenesis of craniofacial muscles. Dev Dyn 235: 1194–1218.

73. ValasekP, TheisS, KrejciE, GrimM, MainaF, et al. (2010) Somitic origin of the medial border of the mammalian scapula and its homology to the avian scapula blade. J Anat 216: 482–488.

74. SambasivanR, KurataniS, TajbakhshS (2011) An eye on the head: the development and evolution of craniofacial muscles. Development 138: 2401–2415.

75. ReynoldsBC, LemmersRJ, TolmieJ, HowatsonAG, HughesDA (2010) Focal segmental glomerulosclerosis, Coats'-like retinopathy, sensorineural deafness and chromosome 4 duplication: a new association. Pediatr Nephrol (8):1551–1554.

76. TakekuraH, FlucherBE, Franzini-ArmstrongC (2001) Sequential docking, molecular differentiation, and positioning of T-Tubule/SR junctions in developing mouse skeletal muscle. Dev Biol 239: 204–214.

77. CabiancaDS, CasaV, BodegaB, XynosA, GinelliE, et al. (2012) A Long ncRNA Links Copy Number Variation to a Polycomb/Trithorax Epigenetic Switch in FSHD Muscular Dystrophy. Cell (4):819–31.

78. ZengW, de GreefJC, ChenYY, ChienR, KongX, et al. (2009) Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS Genet 5: e1000559.

79. SciontiI, GrecoF, RicciG, GoviM, ArashiroP, et al. (2012) Large-scale population analysis challenges the current criteria for the molecular diagnosis of fascioscapulohumeral muscular dystrophy. Am J Hum Genet 90: 628–635.

80. SciontiI, FabbriG, FiorilloC, RicciG, GrecoF, et al. (2012) Facioscapulohumeral muscular dystrophy: new insights from compound heterozygotes and implication for prenatal genetic counselling. J Med Genet 49: 171–178.

81. FitzsimonsRB (2011) Retinal vascular disease and the pathogenesis of facioscapulohumeral muscular dystrophy. A signalling message from Wnt? Neuromuscul Disord 21: 263–271.

82. PadbergGW, BrouwerOF, de KeizerRJ, DijkmanG, WijmengaC, et al. (1995) On the significance of retinal vascular disease and hearing loss in facioscapulohumeral muscular dystrophy. Muscle Nerve 2: S73–80.

83. XuQ, WangY, DabdoubA, SmallwoodPM, WilliamsJ, et al. (2004) Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116: 883–895.

84. RobitailleJ, MacDonaldML, KaykasA, SheldahlLC, ZeislerJ, et al. (2002) Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy. Nat Genet 32: 326–330.

85. ChenZY, BattinelliEM, FielderA, BundeyS, SimsK, et al. (1993) A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy. Nat Genet 5: 180–183.

86. GrosJ, SerralboO, MarcelleC (2009) WNT11 acts as a directional cue to organize the elongation of early muscle fibres. Nature 457: 589–593.

87. Le GrandF, JonesAE, SealeV, ScimeA, RudnickiMA (2009) Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells. Cell Stem Cell 4: 535–547.

88. JingL, LefebvreJL, GordonLR, GranatoM (2009) Wnt signals organize synaptic prepattern and axon guidance through the zebrafish unplugged/MuSK receptor. Neuron 61: 721–733.

89. LangD, LuMM, HuangL, EnglekaKA, ZhangM, et al. (2005) Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 433: 884–887.

90. SrinivasS, WatanabeT, LinCS, WilliamCM, TanabeY, et al. (2001) Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol 1: 4.

91. SchwenkF, BaronU, RajewskyK (1995) A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. Nucleic Acids Res 23: 5080–5081.

92. RodriguezCI, BuchholzF, GallowayJ, SequerraR, KasperJ, et al. (2000) High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 25: 139–140.

93. WrightTJ, WijmengaC, ClarkLN, FrantsRR, WilliamsonR, et al. (1993) Fine mapping of the FSHD gene region orientates the rearranged fragment detected by the probe p13E-11. Hum Mol Genet 2: 1673–1678.

94. NguyenKM, WalrafenPP, BernardRM, AttarianSM, PhD,, ChaixCB, et al. (2011) Molecular combing reveals allelic combinations in facioscapulohumeral dystrophy. Annals of Neurology (4):627–33.

95. MainaF, PanteG, HelmbacherF, AndresR, PorthinA, et al. (2001) Coupling Met to specific pathways results in distinct developmental outcomes. Mol Cell 7: 1293–1306.

96. LivakKJ, SchmittgenTD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408.

97. LaiW, ChoudharyV, ParkPJ (2008) CGHweb: a tool for comparing DNA copy number segmentations from multiple algorithms. Bioinformatics 24: 1014–1015.

98. AarskogNK, VedelerCA (2000) Real-time quantitative polymerase chain reaction. A new method that detects both the peripheral myelin protein 22 duplication in Charcot-Marie-Tooth type 1A disease and the peripheral myelin protein 22 deletion in hereditary neuropathy with liability to pressure palsies. Hum Genet 107: 494–498.