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FGFR1-Frs2/3 Signalling Maintains Sensory Progenitors during Inner Ear Hair Cell Formation


Inner ear mechanosensory hair cells transduce sound and balance information. Auditory hair cells emerge from a Sox2-positive sensory patch in the inner ear epithelium, which is progressively restricted during development. This restriction depends on the action of signaling molecules. Fibroblast growth factor (FGF) signalling is important during sensory specification: attenuation of Fgfr1 disrupts cochlear hair cell formation; however, the underlying mechanisms remain unknown. Here we report that in the absence of FGFR1 signaling, the expression of Sox2 within the sensory patch is not maintained. Despite the down-regulation of the prosensory domain markers, p27Kip1, Hey2, and Hes5, progenitors can still exit the cell cycle to form the zone of non-proliferating cells (ZNPC), however the number of cells that form sensory cells is reduced. Analysis of a mutant Fgfr1 allele, unable to bind to the adaptor protein, Frs2/3, indicates that Sox2 maintenance can be regulated by MAP kinase. We suggest that FGF signaling, through the activation of MAP kinase, is necessary for the maintenance of sensory progenitors and commits precursors to sensory cell differentiation in the mammalian cochlea.


Vyšlo v časopise: FGFR1-Frs2/3 Signalling Maintains Sensory Progenitors during Inner Ear Hair Cell Formation. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004118
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004118

Souhrn

Inner ear mechanosensory hair cells transduce sound and balance information. Auditory hair cells emerge from a Sox2-positive sensory patch in the inner ear epithelium, which is progressively restricted during development. This restriction depends on the action of signaling molecules. Fibroblast growth factor (FGF) signalling is important during sensory specification: attenuation of Fgfr1 disrupts cochlear hair cell formation; however, the underlying mechanisms remain unknown. Here we report that in the absence of FGFR1 signaling, the expression of Sox2 within the sensory patch is not maintained. Despite the down-regulation of the prosensory domain markers, p27Kip1, Hey2, and Hes5, progenitors can still exit the cell cycle to form the zone of non-proliferating cells (ZNPC), however the number of cells that form sensory cells is reduced. Analysis of a mutant Fgfr1 allele, unable to bind to the adaptor protein, Frs2/3, indicates that Sox2 maintenance can be regulated by MAP kinase. We suggest that FGF signaling, through the activation of MAP kinase, is necessary for the maintenance of sensory progenitors and commits precursors to sensory cell differentiation in the mammalian cochlea.


Zdroje

1. GrovesAK, FeketeDM (2012) Shaping sound in space: the regulation of inner ear patterning. Development 139: 245–257.

2. KiernanAE, PellingAL, LeungKK, TangAS, BellDM, et al. (2005) Sox2 is required for sensory organ development in the mammalian inner ear. Nature 434: 1031–1035.

3. NevesJ, KamaidA, AlsinaB, GiraldezF (2007) Differential expression of Sox2 and Sox3 in neuronal and sensory progenitors of the developing inner ear of the chick. J Comp Neurol 503: 487–500.

4. DabdoubA, PuligillaC, JonesJM, FritzschB, CheahKS, et al. (2008) Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea. Proc Natl Acad Sci U S A 105: 18396–18401.

5. DaudetN, LewisJ (2005) Two contrasting roles for Notch activity in chick inner ear development: specification of prosensory patches and lateral inhibition of hair-cell differentiation. Development 132: 541–551.

6. KiernanAE, XuJ, GridleyT (2006) The Notch Ligand JAG1 Is Required for Sensory Progenitor Development in the Mammalian Inner Ear. PLoS Genet 2: e4.

7. DaudetN, Ariza-McNaughtonL, LewisJ (2007) Notch signalling is needed to maintain, but not to initiate, the formation of prosensory patches in the chick inner ear. Development 134: 2369–2378.

8. HartmanBH, RehTA, Bermingham-McDonoghO (2010) Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear. Proc Natl Acad Sci U S A 107: 15792–15797.

9. NevesJ, ParadaC, ChamizoM, GiraldezF (2011) Jagged 1 regulates the restriction of Sox2 expression in the developing chicken inner ear: a mechanism for sensory organ specification. Development 138: 735–744.

10. OhyamaT, BaschML, MishinaY, LyonsKM, SegilN, et al. (2010) BMP signaling is necessary for patterning the sensory and nonsensory regions of the developing mammalian cochlea. J Neurosci 30: 15044–15051.

11. ChenP, SegilN (1999) p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. Development 126: 1581–1590.

12. LeeYS, LiuF, SegilN (2006) A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development. Development 133: 2817–26.

13. AdamJ, MyatA, Le RouxI, EddisonM, HenriqueD, et al. (1998) Cell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development. Development 125: 4645–4654.

14. BrookerR, HozumiK, LewisJ (2006) Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear. Development 133: 1277–1286.

15. LanfordPJ, LanY, JiangR, LindsellC, WeinmasterG, et al. (1999) Notch signalling pathway mediates hair cell development in mammalian cochlea. Nat Genet 21: 289–292.

16. WoodsC, MontcouquiolM, KelleyMW (2004) Math1 regulates development of the sensory epithelium in the mammalian cochlea. Nat Neurosci 7: 1310–1318.

17. DriverEC, SillersL, CoateTM, RoseMF, KelleyMW (2013) The Atoh1-lineage gives rise to hair cells and supporting cells within the mammalian cochlea. Dev Biol 376: 86–98.

18. BerminghamNA, HassanBA, PriceSD, VollrathMA, Ben-ArieN, et al. (1999) Math1: an essential gene for the generation of inner ear hair cells. Science 284: 1837–1841.

19. ChenP, JohnsonJE, ZoghbiHY, SegilN (2002) The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination. Development 129: 2495–2505.

20. PirvolaU, YlikoskiJ, TrokovicR, HebertJM, McConnellSK, et al. (2002) FGFR1 is required for the development of the auditory sensory epithelium. Neuron 35: 671–680.

21. HuhSH, JonesJ, WarcholME, OrnitzDM (2011) Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal. PLoS Biol 10: e1001231.

22. MunnamalaiV, HayashiT, Bermingham-McDonoghO (2012) Notch prosensory effects in the Mammalian cochlea are partially mediated by Fgf20. J Neurosci 32: 12876–12884.

23. TurnerN, GroseR (2010) Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 10: 116–129.

24. MohammadiM, DionneCA, LiW, LiN, SpivakT, et al. (1992) Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis. Nature 358: 681–684.

25. KouharaH, HadariYR, Spivak-KroizmanT, SchillingJ, Bar-SagiD, et al. (1997) A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell 89: 693–702.

26. OngSH, HadariYR, GotohN, GuyGR, SchlessingerJ, et al. (2001) Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins. Proc Natl Acad Sci U S A 98: 6074–6079.

27. GotohN (2008) Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins. Cancer Sci 99: 1319–1325.

28. HochRV, SorianoP (2006) Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development. Development 133: 663–673.

29. MorsliH, ChooD, RyanA, JohnsonR, WuDK (1998) Development of the mouse inner ear and origin of its sensory organs. J Neurosci 18: 3327–3335.

30. PartanenJ, SchwartzL, RossantJ (1998) Opposite phenotypes of hypomorphic and Y766 phosphorylation site mutations reveal a function for Fgfr1 in anteroposterior patterning of mouse embryos. Genes Dev 12: 2332–2344.

31. Bermingham-McDonoghO, OesterleEC, StoneJS, HumeCR, HuynhHM, et al. (2006) Expression of Prox1 during mouse cochlear development. J Comp Neurol 496: 172–186.

32. AhmedM, WongEY, SunJ, XuJ, WangF, et al. (2012) Eya1-Six1 interaction is sufficient to induce hair cell fate in the cochlea by activating Atoh1 expression in cooperation with Sox2. Dev Cell 22: 377–390.

33. YungY, DolginovY, YaoZ, RubinfeldH, MichaelD, et al. (1997) Detection of ERK activation by a novel monoclonal antibody. FEBS Lett 408: 292–296.

34. JacquesBE, MontcouquiolME, LaymanEM, LewandoskiM, KelleyMW (2007) Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian cochlea. Development 134: 3021–3029.

35. HayashiT, CunninghamD, Bermingham-McDonoghO (2007) Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti. Dev Dyn 236: 525–533.

36. ChenP, ZindyF, AbdalaC, LiuF, LiX, et al. (2003) Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nat Cell Biol 5: 422–426.

37. QueJ, OkuboT, GoldenringJR, NamKT, KurotaniR, et al. (2007) Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm. Development 134: 2521–2531.

38. IshiiY, WeinbergK, Oda-IshiiI, CoughlinL, MikawaT (2009) Morphogenesis and cytodifferentiation of the avian retinal pigmented epithelium require downregulation of Group B1 Sox genes. Development 136: 2579–2589.

39. TakemotoT, UchikawaM, KamachiY, KondohH (2006) Convergence of Wnt and FGF signals in the genesis of posterior neural plate through activation of the Sox2 enhancer N-1. Development 133: 297–306.

40. MansukhaniA, AmbrosettiD, HolmesG, CornivelliL, BasilicoC (2005) Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. J Cell Biol 168: 1065–1076.

41. TaranovaOV, MagnessST, FaganBM, WuY, SurzenkoN, et al. (2006) SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev 20: 1187–1202.

42. OkuboT, PevnyLH, HoganBL (2006) Sox2 is required for development of taste bud sensory cells. Genes Dev 20: 2654–2659.

43. BergslandM, RamskoldD, ZaouterC, KlumS, SandbergR, et al. (2011) Sequentially acting Sox transcription factors in neural lineage development. Genes Dev 25: 2453–2464.

44. LiberD, DomaschenzR, HolmqvistPH, MazzarellaL, GeorgiouA, et al. (2010) Epigenetic priming of a pre-B cell-specific enhancer through binding of Sox2 and Foxd3 at the ESC stage. Cell Stem Cell 7: 114–126.

45. NevesJ, UchikawaM, BigasA, GiraldezF (2012) The prosensory function of Sox2 in the chicken inner ear relies on the direct regulation of Atoh1. PLoS One 7: e30871.

46. JonesC, ChenP (2007) Planar cell polarity signaling in vertebrates. Bioessays 29: 120–132.

47. YamamotoN, OkanoT, MaX, AdelsteinRS, KelleyMW (2009) Myosin II regulates extension, growth and patterning in the mammalian cochlear duct. Development 136: 1977–1986.

48. HayashiT, RayCA, Bermingham-McDonoghO (2008) Fgf20 is required for sensory epithelial specification in the developing cochlea. J Neurosci 28: 5991–5999.

49. KawakamiT, KawcakT, LiYJ, ZhangW, HuY, et al. (2002) Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling. Development 129: 5753–5765.

50. PirvolaU, ZhangX, MantelaJ, OrnitzDM, YlikoskiJ (2004) Fgf9 signaling regulates inner ear morphogenesis through epithelial-mesenchymal interactions. Dev Biol 273: 350–360.

51. WrightTJ, HatchEP, KarabagliH, KarabagliP, SchoenwolfGC, et al. (2003) Expression of mouse fibroblast growth factor and fibroblast growth factor receptor genes during early inner ear development. Dev Dyn 228: 267–272.

52. WrightTJ, MansourSL (2003) Fgf3 and Fgf10 are required for mouse otic placode induction. Development 130: 3379–3390.

53. HatchEP, NoyesCA, WangX, WrightTJ, MansourSL (2007) Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium. Development 134: 3615–3625.

54. KumarM, ChapmanSC (2012) Cloning and expression analysis of Fgf5, 6 and 7 during early chick development. Gene Expr Patterns 12: 245–253.

55. OrnitzDM, XuJ, ColvinJS, McEwenDG, MacArthurCA, et al. (1996) Receptor specificity of the fibroblast growth factor family. J Biol Chem 271: 15292–15297.

56. ZhangX, IbrahimiOA, OlsenSK, UmemoriH, MohammadiM, et al. (2006) Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem 281: 15694–15700.

57. ReillyJF, MickeyG, MaherPA (2000) Association of fibroblast growth factor receptor 1 with the adaptor protein Grb14. Characterization of a new receptor binding partner. J Biol Chem 275: 7771–7778.

58. DunicanDJ, WilliamsEJ, HowellFV, DohertyP (2001) Selective inhibition of fibroblast growth factor (FGF)-stimulated mitogenesis by a FGF receptor-1-derived phosphopeptide. Cell Growth Differ 12: 255–264.

59. LarssonH, KlintP, LandgrenE, Claesson-WelshL (1999) Fibroblast growth factor receptor-1-mediated endothelial cell proliferation is dependent on the Src homology (SH) 2/SH3 domain-containing adaptor protein Crk. J Biol Chem 274: 25726–25734.

60. PirvolaU, Spencer-DeneB, Xing-QunL, KettunenP, ThesleffI, et al. (2000) FGF/FGFR-2(IIIb) signaling is essential for inner ear morphogenesis. J Neurosci 20: 6125–6134.

61. SatoS, IkedaK, ShioiG, NakaoK, YajimaH, et al. (2012) Regulation of Six1 expression by evolutionarily conserved enhancers in tetrapods. Dev Biol 368: 95–108.

62. SorianoP (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21: 70–71.

63. LumpkinEA, CollissonT, ParabP, Omer-AbdallaA, HaeberleH, et al. (2003) Math1-driven GFP expression in the developing nervous system of transgenic mice. Gene Expr Patterns 3: 389–395.

64. KimuraJ, SudaY, KurokawaD, HossainZM, NakamuraM, et al. (2005) Emx2 and Pax6 function in cooperation with Otx2 and Otx1 to develop caudal forebrain primordium that includes future archipallium. J Neurosci 25: 5097–5108.

65. HebertJM, McConnellSK (2000) Targeting of cre to the Foxg1 (BF-1) locus mediates loxP recombination in the telencephalon and other developing head structures. Dev Biol 222: 296–306.

66. YamamotoS, YoshinoI, ShimazakiT, MurohashiM, HevnerRF, et al. (2005) Essential role of Shp2-binding sites on FRS2alpha for corticogenesis and for FGF2-dependent proliferation of neural progenitor cells. Proc Natl Acad Sci U S A 102: 15983–15988.

67. TeraokaME, PaschakiM, MutaY, LadherRK (2009) Rostral paraxial mesoderm regulates refinement of the eye field through the bone morphogenetic protein (BMP) pathway. Dev Biol 330: 389–398.

68. LunnJS, FishwickKJ, HalleyPA, StoreyKG (2007) A spatial and temporal map of FGF/Erk1/2 activity and response repertoires in the early chick embryo. Dev Biol 302: 536–552.

69. O'NeillP, MakSS, FritzschB, LadherRK, BakerCV (2012) The amniote paratympanic organ develops from a previously undiscovered sensory placode. Nat Commun 3: 1041.

70. SakamotoT, ItoJ, LadherRK (2007) Hair cell differentiation becomes tissue specific by E9.5 in mouse inner ear. Neuroreport 18: 841–844.

71. YamamotoN, ChangW, KelleyMW (2011) Rbpj regulates development of prosensory cells in the mammalian inner ear. Dev Biol 353: 367–379.

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