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RA and FGF Signalling Are Required in the Zebrafish Otic Vesicle to Pattern and Maintain Ventral Otic Identities


The vertebrate inner ear is a complex three-dimensional structure with hearing and balance functions. To form a functional ear in the embryo, it is crucial that the right cells develop at the right time and in the right place. These cells include the sensory hair cells that detect sound and movement, neurons that relay sensory information to the brain, and structural cells. We have investigated patterning and maintenance events in the developing ear of the zebrafish embryo. We show that two signalling pathways, FGF and Retinoic Acid (RA), act in an antagonistic manner to regulate the numbers of sensory hair cells that develop, together with the expression of a key gene, otx1b, required for the development of structural cells. However, the two signalling pathways act in concert to regulate the emergence of neuronal cells. Our data also indicate that FGF and RA signalling form a feedback loop, placing them at the heart of the regulatory network that ensures correct patterning is maintained in the ear. Both FGF and RA signalling are employed to generate hair cells and neurons for replacement therapies to treat hearing loss. Understanding the roles of FGF and RA signalling underpins the development of such therapies.


Vyšlo v časopise: RA and FGF Signalling Are Required in the Zebrafish Otic Vesicle to Pattern and Maintain Ventral Otic Identities. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004858
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004858

Souhrn

The vertebrate inner ear is a complex three-dimensional structure with hearing and balance functions. To form a functional ear in the embryo, it is crucial that the right cells develop at the right time and in the right place. These cells include the sensory hair cells that detect sound and movement, neurons that relay sensory information to the brain, and structural cells. We have investigated patterning and maintenance events in the developing ear of the zebrafish embryo. We show that two signalling pathways, FGF and Retinoic Acid (RA), act in an antagonistic manner to regulate the numbers of sensory hair cells that develop, together with the expression of a key gene, otx1b, required for the development of structural cells. However, the two signalling pathways act in concert to regulate the emergence of neuronal cells. Our data also indicate that FGF and RA signalling form a feedback loop, placing them at the heart of the regulatory network that ensures correct patterning is maintained in the ear. Both FGF and RA signalling are employed to generate hair cells and neurons for replacement therapies to treat hearing loss. Understanding the roles of FGF and RA signalling underpins the development of such therapies.


Zdroje

1. RaftS, NowotschinS, LiaoJ, MorrowBE (2004) Suppression of neural fate and control of inner ear morphogenesis by Tbx1. Development 131: 1801–1812.

2. RadosevicM, Robert-MorenoA, CoolenM, Bally-CuifL, AlsinaB (2011) Her9 represses neurogenic fate downstream of Tbx1 and retinoic acid signaling in the inner ear. Development 138: 397–408.

3. LiY, AllendeML, FinkelsteinR, WeinbergES (1994) Expression of two zebrafish orthodenticle-related genes in the embryonic brain. Mech Dev 48: 229–244.

4. MercierP, SimeoneA, CotelliF, BoncinelliE (1995) Expression pattern of two otx genes suggests a role in specifying anterior body structures in zebrafish. Int J Dev Biol 39: 559–573.

5. ThisseB, PflumioS, FürthauerM, LoppinB, HeyerV, et al. (2001) Expression of the zebrafish genome during embryogenesis. ZFIN Direct Data Submission

6. HammondKL, WhitfieldTT (2006) The developing lamprey ear closely resembles the zebrafish otic vesicle: otx1 expression can account for all major patterning differences. Development 133: 1347–1357.

7. WhitfieldTT, GranatoM, van EedenFJM, SchachU, BrandM, et al. (1996) Mutations affecting development of the zebrafish inner ear and lateral line. Development 123: 241–254.

8. LégerS, BrandM (2002) Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear patterning. Mech Dev 119: 91–108.

9. LiuD, ChuH, MavesL, YanY-L, MorcosPA, et al. (2003) Fgf3 and Fgf8 dependent and independent transcription factors are required for otic placode specification. Development 130: 2213–2224.

10. MaroonH, WalsheJ, MahmoodR, KieferP, DicksonC, et al. (2002) Fgf3 and Fgf8 are required together for formation of the otic placode and vesicle. Development 129: 2099–2108.

11. PhillipsBT, BoldingK, RileyBB (2001) Zebrafish fgf3 and fgf8 encode redundant functions required for otic placode induction. Dev Biol 235: 351–365.

12. HammondKL, WhitfieldTT (2011) Fgf and Hh signalling act on a symmetrical pre-pattern to specify anterior and posterior identity in the zebrafish otic placode and vesicle. Development 138: 3977–3987.

13. AlsinaB, AbellóG, UlloaE, HenriqueD, PujadesC, et al. (2004) FGF signaling is required for determination of otic neuroblasts in the chick embryo. Dev Biol 267: 119–134.

14. VemarajuS, KantarciH, PadanadMS, RileyBB (2012) A spatial and temporal gradient of Fgf differentially regulates distinct stages of neural development in the zebrafish inner ear. PLoS Genet 8: e1003068.

15. MaierE, SaxenaA, AlsinaB, BronnerM, WhitfieldT (2014) Sensational placodes: Neurogenesis in the otic and olfactory systems. Dev Biol 389: 50–67.

16. HansS, WesterfieldM (2007) Changes in retinoic acid signaling alter otic patterning. Development 134: 2449–2458.

17. GrandelH, LunK, RauchGJ, RhinnM, PiotrowskiT, et al. (2002) Retinoic acid signalling in the zebrafish embryo is necessary during pre-segmentation stages to pattern the anterior-posterior axis of the CNS and to induce a pectoral fin bud. Development 129: 2851–2865.

18. BegemannG, SchillingTF, RauchG-J, GeislerR, InghamPW (2001) The zebrafish neckless mutation reveals a requirement for raldh2 in mesodermal signals that pattern the hindbrain. Development 128: 3081–3094.

19. PittlikS, DominguesS, MeyerA, BegemannG (2008) Expression of zebrafish aldh1a3 (raldh3) and absence of aldh1a1 in teleosts. Gene Exp Patt 8: 141–147.

20. GuX, XuF, WangX, GaoX, ZhaoQ (2005) Molecular cloning and expression of a novel CYP26 gene (cyp26d1) during zebrafish early development. Gene Exp Patt 5: 733–739.

21. MohammadiM, McMahonG, SunL, TangC, HirthP, et al. (1997) Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 276: 955–960.

22. RaibleF, BrandM (2001) Tight transcriptional control of the ETS domain factors Erm and Pea3 by Fgf signaling during early zebrafish development. Mech Dev 107: 105–117.

23. OrnitzD, XuJ, ColvinJ, McEwenD, MacArthurC, et al. (1996) Receptor specificity of the fibroblast growth factor family. J Biol Chem 271: 15292–15297.

24. ReifersF, BöhliH, WalshEC, CrossleyPH, StainierDYR, et al. (1998) Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis. Development 125: 2381–2396.

25. HerzogW, SonntagC, von der HardtS, RoehlHH, VargaZM, et al. (2004) Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis. Development 131: 3681–3692.

26. MillimakiBB, SweetEM, DhasonMS, RileyBB (2007) Zebrafish atoh1 genes: classic proneural activity in the inner ear and regulation by Fgf and Notch. Development 134: 295–305.

27. SweetEM, VemarajuS, RileyBB (2011) Sox2 and Fgf interact with Atoh1 to promote sensory competence throughout the zebrafish inner ear. Dev Biol 358: 113–121.

28. Giuliani G (2011) The role of tbx1 and otx1 in the development of the zebrafish inner ear. PhD thesis, University of Sheffield.

29. BokJ, RaftS, KongKA, KooSK, DrägerUC, et al. (2011) Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear. Proc Natl Acad Sci USA 108: 161–166.

30. BokJ, Bronner-FraserM, WuDK (2005) Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear. Development 132: 2115–2124.

31. BlenticA, GaleE, MadenM (2003) Retinoic acid signalling centres in the avian embryo identified by sites of expression of synthesising and catabolising enzymes. Dev Dyn 227: 114–127.

32. CañestroC, CatchenJ, Rodríguez-MaríA, YokoiH, PostlethwaitJ (2009) Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes. PLoS Genet 5: e1000496.

33. HansS, IrmscherA, BrandM (2013) Zebrafish Foxi1 provides a neuronal ground state during inner ear induction preceding the Dlx3b/4b-regulated sensory lineage. Development 140: 1936–1945.

34. ItohN, OrnitzD (2004) Evolution of the Fgf and Fgfr gene families. Trends Genet 20: 563–569.

35. 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.

36. ColvinJ, BohneB, HardingG, McEwenD, OrnitzD (1996) Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. Nat Genet 12: 390–397.

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

38. MuellerK, JacquesB, KelleyM (2002) Fibroblast growth factor signaling regulates pillar cell development in the organ of Corti. J Neurosci 22: 9368–9377.

39. ShimK, MinowadaG, ColingD, MartinG (2005) Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Dev Cell 8: 553–564.

40. 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.

41. ZelarayanLC, VendrellV, AlvarezY, Domínguez-FrutosE, TheilT, et al. (2007) Differential requirements for FGF3, FGF8 and FGF10 during inner ear development. Dev Biol 308: 379–391.

42. RomandR, HashinoE, DolléP, VoneschJ, ChambonP, et al. (2002) The retinoic acid receptors RARalpha and RARgamma are required for inner ear development. Mech Dev 119: 213–223.

43. FrenzD, LiuW, CveklA, XieQ, WassefL, et al. (2010) Retinoid signaling in inner ear development: A “Goldilocks” phenomenon. Am J Med Genet A 152A: 2947–2961.

44. CadotS, FrenzD, MaconochieM (2012) A novel method for retinoic acid administration reveals differential and dose-dependent downregulation of Fgf3 in the developing inner ear and anterior CNS. Dev Dyn 241: 741–758.

45. Abu-AbedS, DolléP, MetzgerD, WoodC, MacLeanG, et al. (2003) Developing with lethal RA levels: genetic ablation of Rarg can restore the viability of mice lacking Cyp26a1. Development 130: 1449–1459.

46. Diez del CorralR, Olivera-MartinezI, GorielyA, GaleE, MadenM, et al. (2003) Opposing FGF and retinoid pathways control ventral neural pattern, neuronal differentiation, and segmentation during body axis extension. Neuron 40: 65–79.

47. MarklundM, SjödalM, BeehlerB, JessellT, EdlundT, et al. (2004) Retinoic acid signalling specifies intermediate character in the developing telencephalon. Development 131: 4323–4332.

48. Martínez-MoralesP, Diez del CorralR, Olivera-MartínezI, QuirogaA, DasR, et al. (2011) FGF and retinoic acid activity gradients control the timing of neural crest cell emigration in the trunk. J Cell Biol 194: 489–503.

49. BrandM, HeisenbergC-P, JiangY-J, BeuchleD, LunK, et al. (1996) Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain. Development 123: 179–190.

50. ListerJA, RobertsonCP, LepageT, JohnsonSL, RaibleDW (1999) nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. Development 126: 3757–3767.

51. PiotrowskiT, AhnD-G, SchillingTF, NairS, RuvinskyI, et al. (2003) The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans. Development 130: 5043–5052.

52. KikuchiK, HoldwayJE, MajorRJ, BlumN, DahnRD, et al. (2011) Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Dev Cell 20: 397–404.

53. LecaudeyV, Cakan-AkdoganG, NortonWH, GilmourD (2008) Dynamic Fgf signaling couples morphogenesis and migration in the zebrafish lateral line primordium. Development 135: 2695–2705.

54. XiaoT, RoeserT, StaubW, BaierH (2005) A GFP-based genetic screen reveals mutations that disrupt the architecture of the zebrafish retinotectal projection. Development 132: 2955–2967.

55. KimmelCB, BallardWW, KimmelSR, UllmannB, SchillingTF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203: 253–310.

56. Westerfield M (2000) The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio). Eugene: University of Oregon Press.

57. MaA, ChungM, LiangR, LeungA (2010) A DEAB-sensitive aldehyde dehydrogenase regulates hematopoietic stem and progenitor cells development during primitive hematopoiesis in zebrafish embryos. Leukemia 24: 2090–2099.

58. Nüsslein-Volhard C, Dahm R, editors(2002) Zebrafish: A Practical Approach: Oxford University Press.

59. OxtobyE, JowettT (1993) Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development. Nuc Acids Res 21: 1087–1095.

60. KimCH, BaeYK, YamanakaY, YamashitaS, ShimizuT, et al. (1997) Overexpression of neurogenin induces ectopic expression of HuC in zebrafish. Neurosci Lett 239: 113–116.

61. TsangM, MaegawaS, KiangA, HabasR, WeinbergE, et al. (2004) A role for MKP3 in axial patterning of the zebrafish embryo. Development 131: 2769–2779.

62. MünchbergSR, OberEA, SteinbeisserH (1999) Expression of the Ets transcription factors erm and pea3 in early zebrafish development. Mech Dev 88: 233–236.

63. KwakS-J, PhillipsBT, HeckR, RileyBB (2002) An expanded domain of fgf3 expression in the hindbrain of zebrafish valentino mutants results in mis-patterning of the otic vesicle. Development 129: 5279–5287.

64. GrovesJ, HammondC, HughesS (2005) Fgf8 drives myogenic progression of a novel lateral fast muscle fibre population in zebrafish. Development 132: 4211–4222.

65. NechiporukA, LinboT, RaibleDW (2005) Endoderm-derived Fgf3 is necessary and sufficient for inducing neurogenesis in the epibranchial placodes in zebrafish. Development 132: 3717–3730.

66. InoueA, TakahashiM, HattaK, HottaY, OkamotoH (1994) Developmental regulation of islet-1 mRNA expression during neuronal differentiation in embryonic zebrafish. Dev Dyn 199: 1–11.

67. BladerP, FischerN, GradwohlG, GuillemotF, SträhleU (1997) The activity of Neurogenin1 is controlled by local cues in the zebrafish embryo. Development 124: 4557–4569.

68. AndermannP, UngosJ, RaibleDW (2002) Neurogenin1 defines zebrafish cranial sensory ganglia precursors. Dev Biol 251: 45–58.

69. LinvilleA, RadtkeK, WaxmanJ, YelonD, SchillingT (2009) Combinatorial roles for zebrafish retinoic acid receptors in the hindbrain, limbs and pharyngeal arches. Dev Biol 325: 60–70.

70. CunliffeVT, Casaccia-BonnefilP (2006) Histone deacetylase 1 is essential for oligodendrocyte specification in the zebrafish CNS. Mech Dev 123: 24–30.

71. HaddonC, LewisJ (1996) Early ear development in the embryo of the zebrafish, Danio rerio. J Comp Neurol 365: 113–123.

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