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Assembly of the Auditory Circuitry by a Genetic Network in the Mouse Brainstem


Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem.


Vyšlo v časopise: Assembly of the Auditory Circuitry by a Genetic Network in the Mouse Brainstem. PLoS Genet 9(2): e32767. doi:10.1371/journal.pgen.1003249
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003249

Souhrn

Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem.


Zdroje

1. KieckerC, LumsdenA (2005) Compartments and their boundaries in vertebrate brain development. Nat Rev Neurosci 6: 553–564.

2. ClarkeJD, LumsdenA (1993) Segmental repetition of neuronal phenotype sets in the chick embryo hindbrain. Development 118: 151–162.

3. MarinF, PuellesL (1995) Morphological fate of rhombomeres in quail/chick chimeras: a segmental analysis of hindbrain nuclei. Eur J Neurosci 7: 1714–1738.

4. PasqualettiM, DiazC, RenaudJS, RijliFM, GloverJC (2007) Fate-mapping the mammalian hindbrain: segmental origins of vestibular projection neurons assessed using rhombomere-specific Hoxa2 enhancer elements in the mouse embryo. J Neurosci 27: 9670–9681.

5. CramerKS, FraserSE, RubelEW (2000) Embryonic origins of auditory brain-stem nuclei in the chick hindbrain. Dev Biol 224: 138–151.

6. FaragoAF, AwatramaniRB, DymeckiSM (2006) Assembly of the brainstem cochlear nuclear complex is revealed by intersectional and subtractive genetic fate maps. Neuron 50: 205–218.

7. OuryF, MurakamiY, RenaudJS, PasqualettiM, CharnayP, et al. (2006) Hoxa2- and rhombomere-dependent development of the mouse facial somatosensory map. Science 313: 1408–1413.

8. CambroneroF, PuellesL (2000) Rostrocaudal nuclear relationships in the avian medulla oblongata: a fate map with quail chick chimeras. J Comp Neurol 427: 522–545.

9. DiazC, GloverJC, PuellesL, BjaalieJG (2003) The relationship between hodological and cytoarchitectonic organization in the vestibular complex of the 11-day chicken embryo. J Comp Neurol 457: 87–105.

10. Malmierca MS, Merchan MA (2004) Auditory System. In: Paxinos G, editor. The Rat Nervous System. Third Edition ed. San Diego, USA: Elsevier Academic Press. pp. 997–1082.

11. FettiplaceR, HackneyCM (2006) The sensory and motor roles of auditory hair cells. Nat Rev Neurosci 7: 19–29.

12. DallosP (2008) Cochlear amplification, outer hair cells and prestin. Curr Opin Neurobiol 18: 370–376.

13. RubelEW, FritzschB (2002) Auditory system development: primary auditory neurons and their targets. Annu Rev Neurosci 25: 51–101.

14. NicholsDH, BruceLL (2006) Migratory routes and fates of cells transcribing the Wnt-1 gene in the murine hindbrain. Dev Dyn 235: 285–300.

15. FujiyamaT, YamadaM, TeraoM, TerashimaT, HiokiH, et al. (2009) Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1. Development 136: 2049–2058.

16. MaricichSM, XiaA, MathesEL, WangVY, OghalaiJS, et al. (2009) Atoh1-lineal neurons are required for hearing and for the survival of neurons in the spiral ganglion and brainstem accessory auditory nuclei. J Neurosci 29: 11123–11133.

17. WangVY, RoseMF, ZoghbiHY (2005) Math1 expression redefines the rhombic lip derivatives and reveals novel lineages within the brainstem and cerebellum. Neuron 48: 31–43.

18. Willott J (2001). Handbook of Mouse Auditory Research:From Behavior to Molecular Biology: Boca Raton:CRC Press.

19. RoseMF, AhmadKA, ThallerC, ZoghbiHY (2009) Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for Math1. Proc Natl Acad Sci U S A 106: 22462–22467.

20. BruceLL, KingsleyJ, NicholsDH, FritzschB (1997) The development of vestibulocochlear efferents and cochlear afferents in mice. Int J Dev Neurosci 15: 671–692.

21. SimmonsDD (2002) Development of the inner ear efferent system across vertebrate species. J Neurobiol 53: 228–250.

22. DarrowKN, MaisonSF, LibermanMC (2007) Selective removal of lateral olivocochlear efferents increases vulnerability to acute acoustic injury. J Neurophysiol 97: 1775–1785.

23. BrownMC, de VeneciaRK, GuinanJJJr (2003) Responses of medial olivocochlear neurons. Specifying the central pathways of the medial olivocochlear reflex. Exp Brain Res 153: 491–498.

24. de VeneciaRK, LibermanMC, GuinanJJJr, BrownMC (2005) Medial olivocochlear reflex interneurons are located in the posteroventral cochlear nucleus: a kainic acid lesion study in guinea pigs. J Comp Neurol 487: 345–360.

25. GuinanJJJr (2006) Olivocochlear efferents: anatomy, physiology, function, and the measurement of efferent effects in humans. Ear Hear 27: 589–607.

26. GuinanJJJr (2010) Cochlear efferent innervation and function. Curr Opin Otolaryngol Head Neck Surg 18: 447–453.

27. GuinanJJJr, StankovicKM (1996) Medial efferent inhibition produces the largest equivalent attenuations at moderate to high sound levels in cat auditory-nerve fibers. J Acoust Soc Am 100: 1680–1690.

28. WalshEJ, McGeeJ, McFaddenSL, LibermanMC (1998) Long-term effects of sectioning the olivocochlear bundle in neonatal cats. J Neurosci 18: 3859–3869.

29. LeeDJ, de VeneciaRK, GuinanJJJr, BrownMC (2006) Central auditory pathways mediating the rat middle ear muscle reflexes. Anat Rec A Discov Mol Cell Evol Biol 288: 358–369.

30. LibermanMC, GuinanJJJr (1998) Feedback control of the auditory periphery: anti-masking effects of middle ear muscles vs. olivocochlear efferents. J Commun Disord 31: 471–482; quiz 483; 553.

31. KujawaSG, LibermanMC (1997) Conditioning-related protection from acoustic injury: effects of chronic deefferentation and sham surgery. J Neurophysiol 78: 3095–3106.

32. MaisonSF, LuebkeAE, LibermanMC, ZuoJ (2002) Efferent protection from acoustic injury is mediated via alpha9 nicotinic acetylcholine receptors on outer hair cells. J Neurosci 22: 10838–10846.

33. KrumlaufR, MarshallH, StuderM, NonchevS, ShamMH, et al. (1993) Hox homeobox genes and regionalisation of the nervous system. J Neurobiol 24: 1328–1340.

34. TumpelS, WiedemannLM, KrumlaufR (2009) Hox genes and segmentation of the vertebrate hindbrain. Curr Top Dev Biol 88: 103–137.

35. GeisenMJ, Di MeglioT, PasqualettiM, DucretS, BrunetJF, et al. (2008) Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling. PLoS Biol 6: e142 doi:10.1371/journal.pbio.0060142.

36. NaritaY, RijliFM (2009) Hox genes in neural patterning and circuit formation in the mouse hindbrain. Curr Top Dev Biol 88: 139–167.

37. GavalasA, RuhrbergC, LivetJ, HendersonCE, KrumlaufR (2003) Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes. Development 130: 5663–5679.

38. MaconochieMK, NonchevS, StuderM, ChanSK, PopperlH, et al. (1997) Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1. Genes Dev 11: 1885–1895.

39. AwatramaniR, SorianoP, RodriguezC, MaiJJ, DymeckiSM (2003) Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation. Nat Genet 35: 70–75.

40. VoiculescuO, CharnayP, Schneider-MaunouryS (2000) Expression pattern of a Krox-20/Cre knock-in allele in the developing hindbrain, bones, and peripheral nervous system. Genesis 26: 123–126.

41. ArenkielBR, GaufoGO, CapecchiMR (2003) Hoxb1 neural crest preferentially form glia of the PNS. Dev Dyn 227: 379–386.

42. StuderM, PopperlH, MarshallH, KuroiwaA, KrumlaufR (1994) Role of a conserved retinoic acid response element in rhombomere restriction of Hoxb-1. Science 265: 1728–1732.

43. 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.

44. StuderM, LumsdenA, Ariza-McNaughtonL, BradleyA, KrumlaufR (1996) Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1. Nature 384: 630–634.

45. GaufoGO, FlodbyP, CapecchiMR (2000) Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways. Development 127: 5343–5354.

46. AuclairF, ValdesN, MarchandR (1996) Rhombomere-specific origin of branchial and visceral motoneurons of the facial nerve in the rat embryo. J Comp Neurol 369: 451–461.

47. KarisA, PataI, van DoorninckJH, GrosveldF, de ZeeuwCI, et al. (2001) Transcription factor GATA-3 alters pathway selection of olivocochlear neurons and affects morphogenesis of the ear. J Comp Neurol 429: 615–630.

48. PataI, StuderM, van DoorninckJH, BriscoeJ, KuuseS, et al. (1999) The transcription factor GATA3 is a downstream effector of Hoxb1 specification in rhombomere 4. Development 126: 5523–5531.

49. BrownMC, LevineJL (2008) Dendrites of medial olivocochlear neurons in mouse. Neuroscience 154: 147–159.

50. GurungB, FritzschB (2004) Time course of embryonic midbrain and thalamic auditory connection development in mice as revealed by carbocyanine dye tracing. J Comp Neurol 479: 309–327.

51. MacholdR, FishellG (2005) Math1 is expressed in temporally discrete pools of cerebellar rhombic-lip neural progenitors. Neuron 48: 17–24.

52. RiquelmeR, SaldanaE, OsenKK, OttersenOP, MerchanMA (2001) Colocalization of GABA and glycine in the ventral nucleus of the lateral lemniscus in rat: an in situ hybridization and semiquantitative immunocytochemical study. J Comp Neurol 432: 409–424.

53. SaulSM, BrzezinskiJAt, AltschulerRA, ShoreSE, RudolphDD, et al. (2008) Math5 expression and function in the central auditory system. Mol Cell Neurosci 37: 153–169.

54. YamasakiT, KawajiK, OnoK, BitoH, HiranoT, et al. (2001) Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum. Development 128: 3133–3144.

55. FrisinaRD, ZettelML, KelleyPE, WaltonJP (1995) Distribution of calbindin D-28k immunoreactivity in the cochlear nucleus of the young adult chinchilla. Hear Res 85: 53–68.

56. PorA, PocsaiK, RusznakZ, SzucsG (2005) Presence and distribution of three calcium binding proteins in projection neurons of the adult rat cochlear nucleus. Brain Res 1039: 63–74.

57. TumpelS, CambroneroF, FerrettiE, BlasiF, WiedemannLM, et al. (2007) Expression of Hoxa2 in rhombomere 4 is regulated by a conserved cross-regulatory mechanism dependent upon Hoxb1. Dev Biol 302: 646–660.

58. BarrowJR, CapecchiMR (1996) Targeted disruption of the Hoxb-2 locus in mice interferes with expression of Hoxb-1 and Hoxb-4. Development 122: 3817–3828.

59. PattynA, VallstedtA, DiasJM, SamadOA, KrumlaufR, et al. (2003) Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors. Genes Dev 17: 729–737.

60. PopperlH, BienzM, StuderM, ChanSK, AparicioS, et al. (1995) Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell 81: 1031–1042.

61. GoddardJM, RosselM, ManleyNR, CapecchiMR (1996) Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development 122: 3217–3228.

62. RenSY, AngrandPO, RijliFM (2002) Targeted insertion results in a rhombomere 2-specific Hoxa2 knockdown and ectopic activation of Hoxa1 expression. Dev Dyn 225: 305–315.

63. RijliFM, DolleP, FraulobV, LeMeurM, ChambonP (1994) Insertion of a targeting construct in a Hoxd-10 allele can influence the control of Hoxd-9 expression. Dev Dyn 201: 366–377.

64. DavenneM, MaconochieMK, NeunR, PattynA, ChambonP, et al. (1999) Hoxa2 and Hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain. Neuron 22: 677–691.

65. RenSY, PasqualettiM, DierichA, Le MeurM, RijliFM (2002) A Hoxa2 mutant conditional allele generated by Flp- and Cre-mediated recombination. Genesis 32: 105–108.

66. GavalasA, DavenneM, LumsdenA, ChambonP, RijliFM (1997) Role of Hoxa-2 in axon pathfinding and rostral hindbrain patterning. Development 124: 3693–3702.

67. TiveronMC, PattynA, HirschMR, BrunetJF (2003) Role of Phox2b and Mash1 in the generation of the vestibular efferent nucleus. Dev Biol 260: 46–57.

68. ZhaoGY, LiZY, ZouHL, HuZL, SongNN, et al. (2008) Expression of the transcription factor GATA3 in the postnatal mouse central nervous system. Neurosci Res 61: 420–428.

69. RijliFM, MarkM, LakkarajuS, DierichA, DolleP, et al. (1993) A homeotic transformation is generated in the rostral branchial region of the head by disruption of Hoxa-2, which acts as a selector gene. Cell 75: 1333–1349.

70. DanielianPS, MuccinoD, RowitchDH, MichaelSK, McMahonAP (1998) Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol 8: 1323–1326.

71. SantagatiF, MinouxM, RenSY, RijliFM (2005) Temporal requirement of Hoxa2 in cranial neural crest skeletal morphogenesis. Development 132: 4927–4936.

72. RenierN, SchonewilleM, GiraudetF, BaduraA, Tessier-LavigneM, et al. (2010) Genetic dissection of the function of hindbrain axonal commissures. PLoS Biol 8: e1000325 doi:10.1371/journal.pbio.1000325.

73. MaisonSF, AdamsJC, LibermanMC (2003) Olivocochlear innervation in the mouse: immunocytochemical maps, crossed versus uncrossed contributions, and transmitter colocalization. J Comp Neurol 455: 406–416.

74. HenryKR (1979) Auditory brainstem volume-conducted responses: origins in the laboratory mouse. J Am Aud Soc 4: 173–178.

75. ShaSH, KanickiA, DootzG, TalaskaAE, HalseyK, et al. (2008) Age-related auditory pathology in the CBA/J mouse. Hear Res 243: 87–94.

76. ZhuX, VasilyevaON, KimS, JacobsonM, RomneyJ, et al. (2007) Auditory efferent feedback system deficits precede age-related hearing loss: contralateral suppression of otoacoustic emissions in mice. J Comp Neurol 503: 593–604.

77. SimonH, LumsdenA (1993) Rhombomere-specific origin of the contralateral vestibulo-acoustic efferent neurons and their migration across the embryonic midline. Neuron 11: 209–220.

78. GlasgowSM, HenkeRM, MacdonaldRJ, WrightCV, JohnsonJE (2005) Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn. Development 132: 5461–5469.

79. HoshinoM, NakamuraS, MoriK, KawauchiT, TeraoM, et al. (2005) Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron 47: 201–213.

80. PascualM, AbasoloI, Mingorance-Le MeurA, MartinezA, Del RioJA, et al. (2007) Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression. Proc Natl Acad Sci U S A 104: 5193–5198.

81. van der WeesJ, van LooijMA, de RuiterMM, EliasH, van der BurgH, et al. (2004) Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder. Neurobiol Dis 16: 169–178.

82. SzetoIY, LeungKK, ShamMH, CheahKS (2009) Utility of HoxB2 enhancer-mediated Cre activity for functional studies in the developing inner ear. Genesis 47: 361–365.

83. PasqualettiM, RenSY, PouletM, LeMeurM, DierichA, et al. (2002) A Hoxa2 knockin allele that expresses EGFP upon conditional Cre-mediated recombination. Genesis 32: 109–111.

84. BreuskinI, BodsonM, ThelenN, ThiryM, BorgsL, et al. (2010) Glial but not neuronal development in the cochleo-vestibular ganglion requires Sox10. J Neurochem 114: 1827–1839.

85. TiveronMC, HirschMR, BrunetJF (1996) The expression pattern of the transcription factor Phox2 delineates synaptic pathways of the autonomic nervous system. J Neurosci 16: 7649–7660.

86. FranzeA, SequinoL, SaulinoC, AttanasioG, MarcianoE (2003) Effect over time of allopurinol on noise-induced hearing loss in guinea pigs. Int J Audiol 42: 227–234.

87. DanielianPS, EchelardY, VassilevaG, McMahonAP (1997) A 5.5-kb enhancer is both necessary and sufficient for regulation of Wnt-1 transcription in vivo. Dev Biol 192: 300–309.

88. BodeJ, SchlakeT, IberM, SchubelerD, SeiblerJ, et al. (2000) The transgeneticist's toolbox: novel methods for the targeted modification of eukaryotic genomes. Biol Chem 381: 801–813.

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