Concise Reviews: Regeneration in Mammalian Cochlea Hair Cells: Help from Supporting Cells Transdifferentiation.

[en] It is commonly assumed that mammalian cochlear cells do not regenerate. Therefore, if hair cells are lost following an injury, no recovery could occur. However, during the first postnatal week, mice harbor some progenitor cells that retain the ability to give rise to new hair cells. These progenitor cells are in fact supporting cells. Upon hair cells loss, those cells are able to generate new hair cells both by direct transdifferentiation or following cell cycle re-entry and differentiation. However, this property of supporting cells is progressively lost after birth. Here, we review the molecular mechanisms that are involved in mammalian hair cell development and regeneration. Manipulating pathways used during development constitute good candidates for inducing hair cell regeneration after injury. Despite these promising studies, there is still no evidence for a recovery following hair cells loss in adult mammals. Stem Cells 2017.

Research Center/Unit :

Giga-Neurosciences - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Franco, Benedicte

Malgrange, Brigitte ; Université de Liège > GIGA - Neurosciences

Language :

English

Title :

Concise Reviews: Regeneration in Mammalian Cochlea Hair Cells: Help from Supporting Cells Transdifferentiation.

Publication date :

2017

Journal title :

Stem Cells

ISSN :

1066-5099

eISSN :

1549-4918

Publisher :

AlphaMed, Durham, United States - North Carolina

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique

Commentary :

Available on ORBi :

since 30 January 2017

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Bibliography

Schlosser G. Induction and specification of cranial placodes. Dev Biol 2006;294:303– 351.
Schimmang T. Expression and functions of FGF ligands during early otic development. Int J Dev Biol 2007;51:473–481.
Alvarez Y, Alonso MT, Vendrell V et al. Requirements for FGF3 and FGF10 during inner ear formation. Development 2003;130: 6329–6338.
Wright TJ, Mansour SL. Fgf3 and Fgf10 are required for mouse otic placode induction. Development 2003;130:3379– 3390.
Pieper M, Ahrens K, Rink E et al. Differential distribution of competence for panpla-codal and neural crest induction to non-neural and neural ectoderm. Development 2012;139:1175–1187.
Reichert S, Randall RA, Hill CS. A BMP regulatory network controls ectodermal cell fate decisions at the neural plate border. Development 2013;140:4435–4444.
Chen J, Streit A. Induction of the inner ear: Stepwise specification of otic fate from multipotent progenitors. Hear Res 2013;297: 3–12.
Ohyama T, Mohamed OA, Taketo MM et al. Wnt signals mediate a fate decision between otic placode and epidermis. Development 2006;133:865–875.
Ladher RK, O’Neill P, Begbie J. From shared lineage to distinct functions: The development of the inner ear and epibranchial placodes. Development 2010;137:1777–1785.
Wright KD, Mahoney Rogers AA, Zhang J et al. Cooperative and independent functions of FGF and Wnt signaling during early inner ear development. BMC Dev Biol 2015;15:33.
Streit A. Extensive cell movements accompany formation of the otic placode. Dev Biol 2002;249:237–254.
Riccomagno MM, Takada S, Epstein DJ. Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes Dev 2005;19: 1612–1623.
Urness LD, Paxton CN, Wang X et al. FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a. Dev Biol 2010;340:595–604.
Ohyama T, Groves AK, Martin K. The first steps towards hearing: Mechanisms of otic placode induction. Int J Dev Biol 2007;51: 463–472.
Ohyama T, Basch ML, Mishina Y et al. BMP signaling is necessary for patterning the sensory and nonsensory regions of the developing mammalian cochlea. J Neurosci 2010;30:15044–15051.
Hartman BH, Reh TA, Bermingham-McDonogh O. Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear. Proc Natl Acad Sci USA 2010;107:15792–15797.
Chen P, Segil N. p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. Development 1999;126:1581–1590.
Liu Z, Walters BJ, Owen T et al. Regulation of p27Kip1 by Sox2 maintains quiescence of inner pillar cells in the murine auditory sensory epithelium. J Neurosci 2012; 32:10530–10540.
Li H, Collado M, Villasante A et al. p27(Kip1) directly represses Sox2 during embryonic stem cell differentiation. Cell Stem Cell 2012;11:845–852.
Dabdoub A, Puligilla C, Jones JM et al. Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea. Proc Natl Acad Sci USA 2008;105:18396–18401.
Puligilla C, Dabdoub A, Brenowitz SD et al. Sox2 induces neuronal formation in the developing mammalian cochlea. J Neurosci 2010;30:714–722.
Puligilla C, Kelley MW. Dual role for Sox2 in specification of sensory competence and regulation of Atoh1 function. Dev Neurobiol 2017;77.
Bryant J, Goodyear RJ, Richardson GP. Sensory organ development in the inner ear: Molecular and cellular mechanisms. Br Med Bull 2002;63:39–57.
Sher AE. The embryonic and postnatal development of the inner ear of the mouse. Acta Otolaryngol Suppl 1971;285:1–77.
Lim DJ, Anniko M. Developmental morphology of the mouse inner ear. A scanning electron microscopic observation. Acta Otolaryngol Suppl 1985;422:1–69.
Zak M, Klis SF, Grolman W. The Wnt and Notch signalling pathways in the developing cochlea: Formation of hair cells and induction of regenerative potential. Int J Dev Neurosci 2015;47:247–258.
Waqas M, Zhang S, He Z et al. Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea. Front Med 2016;10:237–249.
Jahan I, Pan N, Fritzsch B. Opportunities and limits of the one gene approach: The ability of Atoh1 to differentiate and maintain hair cells depends on the molecular context. Front Cell Neurosci 2015;9:26.
Bermingham NA, Hassan BA, Price SD et al. Math1: An essential gene for the generation of inner ear hair cells. Science 1999; 284:1837–1841.
Chen P, Johnson JE, Zoghbi HY et al. The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination. Development 2002;129:2495–2505.
Pan N, Jahan I, Kersigo J et al. Conditional deletion of Atoh1 using Pax2-Cre results in viable mice without differentiated cochlear hair cells that have lost most of the organ of Corti. Hear Res 2011;275:66–80.
Gubbels SP, Woessner DW, Mitchell JC et al. Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer. Nature 2008;455:537–541.
Chonko KT, Jahan I, Stone J et al. Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear. Dev Biol 2013;381:401–410.
Cai T, Seymour ML, Zhang H et al. Conditional deletion of Atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of Corti. J Neurosci 2013;33:10110–10122.
Lanford PJ, Lan Y, Jiang R et al. Notch signalling pathway mediates hair cell development in mammalian cochlea. Nat Genet 1999;21:289–292.
Zine A, Van De Water TR, de Ribaupierre F. Notch signaling regulates the pattern of auditory hair cell differentiation in mammals. Development 2000;127:3373–3383.
Campbell DP, Chrysostomou E, Doetzlhofer A. Canonical Notch signaling plays an instructive role in auditory supporting cell development. Sci Rep 2016;6:19484.
Weston MD, Pierce ML, Rocha-Sanchez S et al. MicroRNA gene expression in the mouse inner ear. Brain Res 2006;1111:95–104.
Li H, Kloosterman W, Fekete DM. Micro-RNA-183 family members regulate sensori-neural fates in the inner ear. J Neurosci 2010;30:3254–3263.
Mencia A, Modamio-Hoybjor S, Redshaw N et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat Genet 2009;41:609–613.
Solda G, Robusto M, Primignani P et al. A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing. Hum Mol Genet 2012;21:577– 585.
Huyghe A, Van den Ackerveken P, Sacheli R et al. MicroRNA-124 regulates cell specification in the cochlea through modulation of Sfrp4/5. Cell Rep 2015;13:31–42.
Jacques BE, Puligilla C, Weichert RM et al. A dual function for canonical Wnt/ beta-catenin signaling in the developing mammalian cochlea. Development 2012;139: 4395–4404.
Shi F, Hu L, Jacques BE et al. b-Catenin is required for hair-cell differentiation in the cochlea. J Neurosci 2014;34:6470–6479.
Shi F, Cheng YF, Wang XL et al. Beta-catenin up-regulates Atoh1 expression in neural progenitor cells by interaction with an Atoh1 3’ enhancer. J Biol Chem 2010;285:392–400.
Hayashi T, Cunningham D, Bermingham-McDonogh O. Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti. Dev Dyn 2007;236:525–533.
Jacques BE, Montcouquiol ME, Layman EM et al. Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian cochlea. Development 2007;134:3021– 3029.
Brignull HR, Raible DW, Stone JS. Feathers and fins: Non-mammalian models for hair cell regeneration. Brain Res 2009;1277:12–23.
Duncan LJ, Mangiardi DA, Matsui JI et al. Differential expression of unconventional myosins in apoptotic and regenerating chick hair cells confirms two regeneration mechanisms. J Comp Neurol 2006;499:691– 701.
Roberson DW, Alosi JA, Cotanche DA. Direct transdifferentiation gives rise to the earliest new hair cells in regenerating avian auditory epithelium. J Neurosci Res 2004;78: 461–471.
Adler HJ, Raphael Y. New hair cells arise from supporting cell conversion in the acoustically damaged chick inner ear. Neurosci Lett 1996;205:17–20.
Shang J, Cafaro J, Nehmer R et al. Supporting cell division is not required for regeneration of auditory hair cells after ototoxic injury in vitro. J Assoc Res Otolaryngol 2010; 11:203–222.
Oshima K, Grimm CM, Corrales CE et al. Differential distribution of stem cells in the auditory and vestibular organs of the inner ear. J Assoc Res Otolaryngol 2007;8:18–31.
Malgrange B, Belachew S, Thiry M et al. Proliferative generation of mammalian auditory hair cells in culture. Mech Dev 2002; 112:79–88.
White PM, Doetzlhofer A, Lee YS et al. Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature 2006;441:984–987.
Sinkkonen ST, Chai R, Jan TA et al. Intrinsic regenerative potential of murine cochlear supporting cells. Sci Rep 2011;1:26.
Chai R, Kuo B, Wang T et al. Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc Natl Acad Sci USA 2012;109:8167–8172.
Shi F, Kempfle JS, Edge AS. Wnt-respon-sive Lgr5-expressing stem cells are hair cell progenitors in the cochlea. J Neurosci 2012; 32:9639–9648.
Cox BC, Chai R, Lenoir A et al. Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development 2014; 141:816–829.
Ni W, Lin C, Guo L et al. Extensive supporting cell proliferation and mitotic hair cell generation by in vivo genetic reprogramming in the neonatal mouse cochlea. J Neurosci 2016;36:8734–8745.
Yun MH. Changes in regenerative capacity through lifespan. Int J Mol Sci 2015;16: 25392–25432.
Walters BJ, Zuo J. Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration. Hear Res 2013;297:68–83.
Li W, Wu J, Yang J et al. Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway. Proc Natl Acad Sci USA 2015;112: 166–171.
Mizutari K, Fujioka M, Hosoya M et al. Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron 2013;77:58–69.
Tona Y, Hamaguchi K, Ishikawa M et al. Therapeutic potential of a gamma-secretase inhibitor for hearing restoration in a guinea pig model with noise-induced hearing loss. BMC Neurosci 2014;15:66.
Maass JC, Gu R, Basch ML et al. Changes in the regulation of the Notch signaling pathway are temporally correlated with regenerative failure in the mouse cochlea. Front Cell Neurosci 2015;9:110.
Shi F, Hu L, Edge AS. Generation of hair cells in neonatal mice by beta-catenin over-expression in Lgr5-positive cochlear progenitors. Proc Natl Acad Sci USA 2013;110: 13851–13856.
Roccio M, Hahnewald S, Perny M et al. Cell cycle reactivation of cochlear progenitor cells in neonatal FUCCI mice by a GSK3 small molecule inhibitor. Sci Rep 2015;5:17886.
Ni W, Zeng S, Li W et al. Wnt activation followed by Notch inhibition promotes mitotic hair cell regeneration in the postnatal mouse cochlea. Oncotarget 2016;7.
Waqas M, Guo L, Zhang S et al. Characterization of Lgr51 progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea. Oncotarget 2016:7.
Liu Z, Dearman JA, Cox BC et al. Age-dependent in vivo conversion of mouse cochlear pillar and Deiters’ cells to immature hair cells by Atoh1 ectopic expression. J Neurosci 2012;32:6600–6610.
Kelly MC, Chang Q, Pan A et al. Atoh1 directs the formation of sensory mosaics and induces cell proliferation in the postnatal mammalian cochlea in vivo. J Neurosci 2012; 32:6699–6710.
Izumikawa M, Minoda R, Kawamoto K et al. Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals. Nat Med 2005;11:271– 276.
Kuo BR, Baldwin EM, Layman WS et al. In vivo cochlear hair cell generation and survival by coactivation of beta-Catenin and Atoh1. J Neurosci 2015;35:10786–10798.
Defourny J, Mateo Sanchez S, Schoonaert L et al. Cochlear supporting cell transdifferentiation and integration into hair cell layers by inhibition of ephrin-B2 signalling. Nat Commun 2015;6:7017.
Grego-Bessa J, Luna-Zurita L, del Monte G et al. Notch signaling is essential for ventricular chamber development. Dev Cell 2007;12:415–429.