Eph/ephrin signalling in the development and function of the mammalian cochlea.

[en] In mammals, the functional development of the cochlea requires the tight regulation of multiple molecules and signalling pathways including fibroblast growth factors, bone morphogenetic proteins, Wnt and Notch signalling pathways. Over the last decade, the Eph/ephrin system also emerged as a key player of the development and function of the mammalian cochlea. In this review, we discuss the recent advances on the role of Eph/ephrin signalling in patterning the cochlear sensory epithelium and the complex innervation of mechanosensory hair cells by spiral ganglion neurons. Finally, we address the issue of a syndromic form of hearing loss caused by a deficient member of the Eph/ephrin family.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Defourny, Jean ; Université de Liège - ULiège > Neurosciences-Cellular and tissular biology

Language :

English

Title :

Eph/ephrin signalling in the development and function of the mammalian cochlea.

Publication date :

2019

Journal title :

Developmental Biology

ISSN :

0012-1606

eISSN :

1095-564X

Publisher :

Elsevier, Atlanta, United States - Florida

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 26 February 2019

Statistics

Number of views

91 (9 by ULiège)

Number of downloads

169 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Adams, R.H., Alitalo, K., Molecular regulation of angiogenesis and lymphangiogenesis. Nat. Rev. Mol. Cell Biol. 8 (2007), 464–478 https://doi.org/10.1038/nrm2183.
Ahmad, S., Chen, S., Sun, J., Lin, X., Connexins 26 and 30 are co-assembled to form gap junctions in the cochlea of mice. Biochem. Biophys. Res. Commun. 307 (2003), 362–368 https://doi.org/10.1016/S0006-291X(03)01166-5.
Bianchi, L.M., Dinsio, K., Davoli, K., Gale, N.W., Lac z histochemistry and immunohistochemistry reveal ephrin-B ligand expression in the inner ear. J. Histochem. Cytochem. 50 (2002), 1641–1645 https://doi.org/10.1177/002215540205001208.
Bianchi, L.M., Gale, N.W., Distribution of Eph-related molecules in the developing and mature cochlea. Hear. Res. 117 (1998), 161–172 https://doi.org/10.1016/S0378-5955(98)00010-0.
Bianchi, L.M., Gray, N.A., EphB receptors influence growth of ephrin-B1-positive statoacoustic nerve fibers. Eur. J. Neurosci. 16 (2002), 1499–1506 https://doi.org/10.1046/j.1460-9568.2002.02248.x.
Bianchi, L.M., Liu, H., Comparison of ephrin-A ligand and EphA receptor distribution in the developing inner ear. Anat. Rec. 254 (1999), 127–134 https://doi.org/10.1002/(SICI)1097-0185(19990101)254:1<127::AID-AR16>3.0.CO;2-Q.
Bochenek, M.L., Dickinson, S., Astin, J.W., Adams, R.H., Nobes, C.D., Ephrin-B2 regulates endothelial cell morphology and motility independently of Eph-receptor binding. J. Cell Sci. 123 (2010), 1235–1246 https://doi.org/10.1242/jcs.061903.
Bowden, T.A., Aricescu, A.R., Nettleship, J.E., Siebold, C., Rahman-Huq, N., Owens, R.J., Stuart, D.I., Jones, E.Y., Structural plasticity of eph receptor A4 facilitates cross-class ephrin signaling. Structure 17 (2009), 1386–1397 https://doi.org/10.1016/j.str.2009.07.018.
Brors, D., Bodmer, D., Pak, K., Aletsee, C., Schäfers, M., Dazert, S., Ryan, A.F., EphA4 provides repulsive signals to developing cochlear ganglion neurites mediated through ephrin-B2 and -B3. J. Comp. Neurol. 462 (2003), 90–100 https://doi.org/10.1002/cne.10707.
Cheng, Y.C., Amoyel, M., Qiu, X., Jiang, Y.J., Xu, Q., Wilkinson, D.G., Notch activation regulates the segregation and differentiation of rhombomere boundary cells in the zebrafish hindbrain. Dev. Cell 6 (2004), 539–550 https://doi.org/10.1016/S1534-5807(04)00097-8.
Clark, D.L., Kreutzberg, J.R., Chee, F.K., Vestibular stimulation influence on motor development in infants. Science 196 (1977), 1228–1229 https://doi.org/10.1126/science.300899.
Coate, T.M., Kelley, M.W., Making connections in the inner ear: recent insights into the development of spiral ganglion neurons and their connectivity with sensory hair cells. Semin. Cell Dev. Biol. 24 (2013), 460–469 https://doi.org/10.1016/j.semcdb.2013.04.003.
Coate, T.M., Raft, S., Zhao, X., Ryan, A.K., Crenshaw, E.B. 3rd, Kelley, M.W., Otic mesenchyme cells regulate spiral ganglion fasciculation through a Pou3f4/EphA4 signaling pathway. Neuron 73 (2012), 49–63 https://doi.org/10.1016/j.neuron.2011.10.029.
Coate, T.M., Scott, M.K., Gurjar, M.C., Current concepts in cochlear ribbon synapse formation. Synapse, 2018 https://doi.org/10.1002/syn.22087.
Cowan, C.A., Yokoyama, N., Bianchi, L.M., Henkemeyer, M., Fritzsch, B., EphB2 guides axons at the midline and is necessary for normal vestibular function. 26, 2000, 417–430 https://doi.org/10.1016/S0896-6273(00)81174-5.
Cramer, K.S., Eph proteins and the assembly of auditory circuits. Hear. Res. 206 (2005), 42–51 https://doi.org/10.1016/j.heares.2004.11.024.
Cramer, K.S., Gabriele, M.L., Axon guidance in the auditory system: multiple functions of Eph receptors. Neuroscience 277 (2014), 152–162 https://doi.org/10.1016/j.neuroscience.2014.06.068.
Davy, A., Bush, J.O., Soriano, P., Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies craniofrontonasal syndrome. PLoS Biol., 4, 2006, e315 https://doi.org/10.1371/journal.pbio.0040315.
Defourny, J., Lallemand, F., Malgrange, B., Structure and development of cochlear afferent innervation in mammals. Am. J. Physiol. Cell Physiol. 301 (2011), C750–C761 https://doi.org/10.1152/ajpcell.00516.2010.
Defourny, J., Mateo Sánchez, S., Schoonaert, L., Robberecht, W., Davy, A., Nguyen, L., Malgrange, B., Cochlear supporting cell transdifferentiation and integration into hair cell layers by inhibition of ephrin-B2 signalling. Nat. Commun., 6, 2015, 7017 https://doi.org/10.1038/ncomms8017.
Defourny, J., Peuckert, C., Kullander, K., Malgrange, B., EphA4-ADAM10 interplay patterns the cochlear sensory epithelium through local disruption of adherens junctions. iScience, 2019 https://doi.org/10.1016/j.isci.2018.12.017.
Defourny, J., Poirrier, A.L., Lallemend, F., Mateo Sánchez, S., Neef, J., Vanderhaeghen, P., Soriano, E., Peuckert, C., Kullander, K., Fritzsch, B., Nguyen, L., Moonen, G., Moser, T., Malgrange, B., Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells. Nat. Commun., 4, 2013, 1438 https://doi.org/10.1038/ncomms2445.
Defourny, J., Thelen, N., Thiry, M., Cochlear connexin 30 homomeric and heteromeric channels exhibit distinct assembly mechanisms. Mech. Dev. 155 (2019), 8–14 https://doi.org/10.1016/j.mod.2018.10.001.
de Kok, Y.J., van der Maarel, S.M., Bitner-Glindzicz, M., Huber, I., Monaco, A.P., Malcolm, S., Pembrey, M.E., Ropers, H.H., Cremers, F.P., Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4. Science 267 (1995), 685–688 https://doi.org/10.1126/science.7839145.
Dravis, C., Wu, T., Chumley, M.J., Yokoyama, N., Wei, S., Du, W.K., Marcus, D.C., Henkemeyer, M., EphB2 and ephrin-B2 regulate the ionic homeostasis of vestibular endolymph. Hear. Res. 223 (2007), 93–104 https://doi.org/10.1016/j.heares.2006.10.007.
Druckenbrod, N.R., Goodrich, L.V., Sequential retraction segregates SGN processes during target selection in the cochlea. J. Neurosci. 35 (2015), 16221–16235 https://doi.org/10.1523/JNEUROSCI.2236-15.2015.
Egea, J., Klein, R., Bidirectional Eph-ephrin signaling during axon guidance. Trends Cell Biol. 17 (2007), 230–238 https://doi.org/10.1016/j.tcb.2007.03.004.
Fekete, D.M., Campero, A.M., Axon guidance in the inner ear. Int. J. Dev. Biol. 51 (2007), 549–556 https://doi.org/10.1387/ijdb.072341df.
Flanagan, J.G., Neural map specification by gradients. Curr. Opin. Neurobiol. 16 (2006), 59–66 https://doi.org/10.1016/j.conb.2006.01.010.
Froud, K.E., Wong, A.C., Cederholm, J.M., Klugmann, M., Sandow, S.L., Julien, J.P., Ryan, A.F., Housley, G.D., Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier. Nat. Commun., 6, 2015, 7115 https://doi.org/10.1038/ncomms8115.
Gale, N.W., Holland, S.J., Valenzuela, D.M., Flenniken, A., Pan, L., Ryan, T.E., Henkemeyer, M., Strebhardt, K., Hirai, H., Wilkinson, D.G., Pawson, T., Davis, S., Yancopoulos, G.D., Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 17 (1996), 9–19 https://doi.org/10.1016/S0896-6273(00)80276-7.
Grifa, A., Wagner, C.A., D'Ambrosio, L., Melchionda, S., Bernardi, F., Lopez-Bigas, N., Rabionet, R., Arbones, M., Monica, M.D., Estivill, X., Zelante, L., Lang, F., Gasparini, P., Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nat. Genet. 23 (1999), 16–18 https://doi.org/10.1038/12612.
Groves, A.K., Fekete, D.M., Shaping sound in space: the regulation of inner ear patterning. Development 139 (2012), 245–257 https://doi.org/10.1242/dev.067074.
Haddon, C., Jiang, Y.J., Smithers, L., Lewis, J., Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant. Development 125 (1998), 4637–4644.
Hirai, H., Maru, Y., Hagiwara, K., Nishida, J., Takaku, F., A novel putative tyrosine kinase receptor encoded by the eph gene. Science 238 (1987), 1717–1720 https://doi.org/10.1126/science.2825356.
Howard, M.A., Rodenas-Ruano, A., Henkemeyer, M., Martin, G.K., Lonsbury-Martin, B.L., Liebl, D.J., Eph receptor deficiencies lead to altered cochlear function. Hear. Res. 178 (2003), 118–130 https://doi.org/10.1016/S0378-5955(03)00068-6.
Huang, L.C., Thorne, P.R., Housley, G.D., Montgomery, J.M., Spatiotemporal definition of neurite outgrowth, refinement and retraction in the developing mouse cochlea. Development 134 (2007), 2925–2933 https://doi.org/10.1242/dev.001925.
Ingham, N.J., Steel, K.P., Drescher, U., On the role of ephrinA2 in auditory function. Hear. Res. 350 (2017), 11–16 https://doi.org/10.1016/j.heares.2017.04.002.
Ito, M., Spicer, S.S., Schulte, B.A., Cytological changes related to maturation of the organ of Corti and opening of Corti's tunnel. Hear. Res. 88 (1995), 107–123 https://doi.org/10.1016/0378-5955(95)00106-E.
Johnen, N., Francart, M.E., Thelen, N., Cloes, M., Thiry, M., Evidence for a partial epithelial-mesenchymal transition in postnatal stages of rat auditory organ morphogenesis. Histochem. Cell Biol. 138 (2012), 477–488 https://doi.org/10.1007/s00418-012-0969-5.
Kania, A., Klein, R., Mechanisms of ephrin-Eph signalling in development, physiology and disease. Nat. Rev. Mol. Cell Biol. 17 (2016), 240–256 https://doi.org/10.1038/nrm.2015.16.
Karavitaki, K.D., Mountain, D.C., Evidence for outer hair cell driven oscillatory fluid flow in the tunnel of corti. Biophys. J. 92 (2007), 3284–3293 https://doi.org/10.1529/biophysj.106.084087.
Kelley, M.W., Regulation of cell fate in the sensory epithelia of the inner ear. Nat. Rev. Neurosci. 7 (2006), 837–849 https://doi.org/10.1038/nrn1987.
Kelsell, D.P., Dunlop, J., Stevens, H.P., Lench, N.J., Liang, J.N., Parry, G., Mueller, R.F., Leigh, I.M., Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 387 (1997), 80–83 https://doi.org/10.1038/387080a0.
Kikuchi, T., Kimura, R.S., Paul, D.L., Takasaka, T., Adams, J.C., Gap junction systems in the mammalian cochlea. Brain Res. Brain Res. Rev. 32 (2000), 163–166 https://doi.org/10.1016/S0165-0173(99)00076-4.
Kim, Y.J., Ibrahim, L.A., Wang, S.Z., Yuan, W., Evgrafov, O.V., Knowles, J.A., Wang, K., Tao, H.W., Zhang, L.I., Epha7 regulates spiral ganglion innervation of cochlear hair cells. Dev. Neurobiol. 76 (2016), 452–469 https://doi.org/10.1002/dneu.22326.
Klein, R., Eph/ephrin signaling in morphogenesis, neural development and plasticity. Curr. Opin. Cell Biol. 16 (2004), 580–589 https://doi.org/10.1016/j.ceb.2004.07.002.
Kullander, K., Klein, R., Mechanisms and functions of Eph and ephrin signalling. Nat. Rev. Mol. Cell Biol. 3 (2002), 475–486 https://doi.org/10.1038/nrm856.
Lanford, P.J., Lan, Y., Jiang, R., Lindsell, C., Weinmaster, G., Gridley, T., Kelley, M.W., Notch signalling pathway mediates hair cell development in mammalian cochlea. Nat. Genet. 21 (1999), 289–292 https://doi.org/10.1038/6804.
Lee, A.M., Navaratnam, D., Ichimiya, S., Greene, M.I., Davis, J.G., Cloning of m-ehk2 from the murine inner ear, an eph family receptor tyrosine kinase expressed in the developing and adult cochlea. DNA Cell Biol. 15 (1996), 817–825 https://doi.org/10.1089/dna.1996.15.817.
Lee, K.H., Warchol, M.E., Pawlowski, K.S., Shao, D., Koulich, E., Zhou, C.Q., Lee, J., Henkemeyer, M.J., Ephrins and Ephs in cochlear innervation and implications for advancing cochlear implant function. Laryngoscope 125 (2015), 1189–1197 https://doi.org/10.1002/lary.25066.
Lévy, J., Haye, D., Marziliano, N., Casu, G., Guimiot, F., Dupont, C., Teissier, N., Benzacken, B., Gressens, P., Pipiras, E., Verloes, A., Tabet, A.C., EFNB2 haploinsufficiency causes a syndromic neurodevelopmental disorder. Clin. Genet. 93 (2018), 1141–1147 https://doi.org/10.1111/cge.13234.
Lisabeth, E.M., Falivelli, G., Pasquale, E.B., Eph receptor signaling and ephrins. Cold Spring Harb. Perspect. Biol., 5, 2013, a009159 https://doi.org/10.1101/cshperspect.a009159.
Magomedova, L., Tiefenbach, J., Zilberman, E., Le Billan, F., Voisin, V., Saikali, M., Boivin, V., Robitaille, M., Gueroussov, S., Irimia, M., Ray, D., Patel, R., Xu, C., Jeyasuria, P., Bader, G.D., Hughes, T.R., Morris, Q.D., Scott, M.S., Krause, H., Angers, S., Blencowe, B.J., Cummins, C.L., ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development. Nucleic Acids Res., 2019 https://doi.org/10.1093/nar/gkz010.
Maison, S., Liberman, L.D., Liberman, M.C., Type II cochlear ganglion neurons do not drive the olivocochlear reflex: re-examination of the cochlear phenotype in peripherin knock-out mice. eNeuro, 3(4), 2016 https://doi.org/10.1523/ENEURO.0207-16.2016.
Mäkinen, T., Adams, R.H., Bailey, J., Lu, Q., Ziemiecki, A., Alitalo, K., Klein, R., Wilkinson, G.A., PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev. 19 (2005), 397–410 https://doi.org/10.1101/gad.330105.
Miko, I.J., Henkemeyer, M., Cramer, K.S., Auditory brainstem responses are impaired in EphA4 and ephrin-B2 deficient mice. Hear. Res. 235 (2008), 39–46 https://doi.org/10.1016/j.heares.2007.09.003.
Minowa, O., Ikeda, K., Sugitani, Y., Oshima, T., Nakai, S., Katori, Y., Suzuki, M., Furukawa, M., Kawase, T., Zheng, Y., Ogura, M., Asada, Y., Watanabe, K., Yamanaka, H., Gotoh, S., Nishi-Takeshima, M., Sugimoto, T., Kikuchi, T., Takasaka, T., Noda, T., Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness. Science 285 (1999), 1408–1411 https://doi.org/10.1126/science.285.5432.1408.
Pasquale, E.B., Eph receptor signalling casts a wide net on cell behaviour. Nat. Rev. Mol. Cell Biol. 6 (2005), 462–475 https://doi.org/10.1038/nrm1662.
Pasquale, E.B., Eph-ephrin bidirectional signaling in physiology and disease. Cell 133 (2008), 38–52 https://doi.org/10.1016/j.cell.2008.03.011.
Petitpré C., Wu, H., Sharma, A., Tokarska, A., Fontanet, P., Wang, Y., Helmbacher, F., Yackle, K., Silberberg, G., Hadjab, S., Lallemend, F., Neuronal heterogeneity and stereotyped connectivity in the auditory afferent system. Nat. Commun., 9, 2018, 3691 https://doi.org/10.1038/s41467-018-06033-3.
Pickles, J.O., Expression of Ephs and ephrins in developing mouse inner ear. Hear. Res. 178 (2003), 44–51 https://doi.org/10.1016/S0378-5955(03)00029-7.
Pickles, J.O., Claxton, C., Van Heumen, W.R., Complementary and layered expression of Ephs and ephrins in developing mouse inner ear. J. Comp. Neurol. 449 (2002), 207–216 https://doi.org/10.1002/cne.10231.
Pirvola, U., Lehtonen, E., Ylikoski, J., Spatiotemporal development of cochlear innervation and hair cell differentiation in the rat. Hear. Res. 52 (1991), 345–355 https://doi.org/10.1016/0378-5955(91)90024-4.
Poliakov, A., Cotrina, M., Wilkinson, D.G., Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly. Dev. Cell 7 (2004), 465–480 https://doi.org/10.1016/j.devcel.2004.09.006.
Qin, H., Noberini, R., Huan, X., Shi, J., Pasquale, E.B., Song, J., Structural characterization of the EphA4-Ephrin-B2 complex reveals new features enabling Eph-ephrin binding promiscuity. J. Biol. Chem. 285 (2010), 644–654 https://doi.org/10.1074/jbc.M109.064824.
Rubel, E.W., Fritzsch, B., Auditory system development: primary auditory neurons and their targets. Annu. Rev. Neurosci. 25 (2002), 51–101 https://doi.org/10.1146/annurev.neuro.25.112701.142849.
Shrestha, B.R., Chia, C., Wu, L., Kujawa, S.G., Liberman, M.C., Goodrich, L.V., Sensory neuron diversity in the inner ear is shaped by activity. Cell 174 (2018), 1229–1246 https://doi.org/10.1016/j.cell.2018.07.007.
Sun, J., Ahmad, S., Chen, S., Tang, W., Zhang, Y., Chen, P., Lin, X., Cochlear gap junctions coassembled from Cx26 and 30 show faster intercellular Ca2+ signaling than homomeric counterparts. Am. J. Physiol. Cell Physiol. 288 (2005), C613–C623 https://doi.org/10.1152/ajpcell.00341.2004.
Sun, S., Babola, T., Pregernig, G., So, K.S., Nguyen, M., Su, S.M., Palermo, A.T., Bergles, D.E., Burns, J.C., Müller, U., Hair cell mechanotransduction regulates spontaneous activity and spiral ganglion subtype specification in the auditory system. Cell 174 (2018), 1247–1263 https://doi.org/10.1016/j.cell.2018.07.008.
Tessier-Lavigne, M., Eph receptor tyrosine kinases, axon repulsion, and the development of topographic maps. Cell 82 (1995), 345–348 https://doi.org/10.1016/0092-8674(95)90421-2.
Van Heumen, W.R., Claxton, C., Pickles, J.O., Expression of EphA4 in developing inner ears of the mouse and guinea pig. Hear. Res. 139 (2000), 42–50 https://doi.org/10.1016/S0378-5955(99)00158-6.
Wangemann, P., K+ cycling and the endocochlear potential. Hear. Res. 165 (2002), 1–9 https://doi.org/10.1016/S0378-5955(02)00279-4.
Wangemann, P., K(+) cycling and its regulation in the cochlea and the vestibular labyrinth. Audiol. Neuro. Otol. 7 (2002), 199–205 https://doi.org/10.1159/000063736.
Whitlon, D.S., E-cadherin in the mature and developing organ of Corti of the mouse. J. Neurocytol. 22 (1993), 1030–1038 https://doi.org/10.1007/BF01235747.
Wilkinson, D.G., Regulation of cell differentiation by Eph receptor and ephrin signaling. Cell Adhes. Migrat. 8 (2014), 339–348 https://doi.org/10.4161/19336918.2014.970007.
Wu, D.K., Kelley, M.W., Molecular mechanisms of inner ear development. Cold Spring Harb. Perspect. Biol., 4, 2012, a008409 https://doi.org/10.1101/cshperspect.a008409.
Yates, N., Robertson, D., Martin-Iverson, M., Rodger, J., Auditory brainstem responses of ephrin-A2, ephrin-A5(-/-) and ephrin-A2A5(-/-) mice. Audiol. Neuro. Otol. 19 (2014), 115–126 https://doi.org/10.1159/000357029.
Zhou, C.Q., Lee, J., Henkemeyer, M.J., Lee, K.H., Disruption of ephrin B/Eph B interaction results in abnormal cochlear innervation patterns. Laryngoscope 121 (2011), 1541–1547 https://doi.org/10.1002/lary.21861.