CLC number: R764.35
On-line Access: 2019-01-22
Received: 2016-12-02
Revision Accepted: 2017-03-26
Crosschecked: 2017-07-13
Cited: 0
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Yen-Fu Cheng. Atoh1 regulation in the cochlea: more than just transcription[J]. Journal of Zhejiang University Science B, 2019, 20(2): 146-155.
@article{title="Atoh1 regulation in the cochlea: more than just transcription",
author="Yen-Fu Cheng",
journal="Journal of Zhejiang University Science B",
volume="20",
number="2",
pages="146-155",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600438"
}
%0 Journal Article
%T Atoh1 regulation in the cochlea: more than just transcription
%A Yen-Fu Cheng
%J Journal of Zhejiang University SCIENCE B
%V 20
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%P 146-155
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600438
TY - JOUR
T1 - Atoh1 regulation in the cochlea: more than just transcription
A1 - Yen-Fu Cheng
J0 - Journal of Zhejiang University Science B
VL - 20
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SP - 146
EP - 155
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600438
Abstract: More than 80% of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons, and a lack of regeneration of these cells leads to permanent hearing loss. Therefore, the regeneration of lost hair cells is an important goal for the treatment of deafness. atoh1 is a basic helix-loop-helix (bHLH) transcription factor that is critical in both the development and regeneration of cochlear hair cells. atoh1 is transcriptionally regulated by several signaling pathways, including Notch and Wnt signalings. At the post-translational level, it is regulated through the ubiquitin-proteasome pathway. In vitro and in vivo studies have revealed that manipulation of these signaling pathways not only controls development, but also leads to the regeneration of cochlear hair cells after damage. Recent progress toward understanding the signaling networks involved in hair cell development and regeneration has led to the development of new strategies to replace lost hair cells. This review focuses on our current understanding of the signaling pathways that regulate atoh1 in the cochlea.
[1]Akil O, Seal RP, Burke K, et al., 2012. Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy. Neuron, 75(2):283-293.
[2]Askew C, Rochat C, Pan B, et al., 2015. Tmc gene therapy restores auditory function in deaf mice. Sci. Transl. Med, 7(295):295ra108.
[3]Atkinson PJ, Wise AK, Flynn BO, et al., 2014. Hair cell regeneration after ATOH1 gene therapy in the cochlea of profoundly deaf adult guinea pigs. PLoS ONE, 9(7):e102077.
[4]Ayrault O, Zhao H, Zindy F, et al., 2010. Atoh1 inhibits neuronal differentiation and collaborates with Gli1 to generate medulloblastoma-initiating cells. Cancer Res, 70(13):5618-5627.
[5]Ben-Arie N, McCall AE, Berkman S, et al., 1996. Evolutionary conservation of sequence and expression of the bHLH protein atonal suggests a conserved role in neurogenesis. Hum. Mol. Genet, 5(9):1207-1216.
[6]Ben-Arie N, Bellen HJ, Armstrong DL, et al., 1997. Math1 is essential for genesis of cerebellar granule neurons. Nature, 390(6656):169-172.
[7]Ben-Arie N, Hassan BA, Bermingham NA, et al., 2000. Functional conservation of atonal and Math1 in the CNS and PNS. Development, 127(5):1039-1048.
[8]Bermingham NA, Hassan BA, Price SD, et al., 1999. Math1: an essential gene for the generation of inner ear hair cells. Science, 284(5421):1837-1841.
[9]Bertrand N, Castro DS, Guillemot F, 2002. Proneural genes and the specification of neural cell types. Nat. Rev. Neurosci, 3(7):517-530.
[10]Bossuyt W, Kazanjian A, de Geest N, et al., 2009. Atonal homolog 1 is a tumor suppressor gene. PLoS Biol, 7(2):e1000039.
[11]Bramhall NF, Shi F, Arnold K, et al., 2014. Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea. Stem Cell Rep, 2(3):311-322.
[12]Brooker R, Hozumi K, Lewis J, 2006. Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear. Development, 133(7):1277-1286.
[13]Cai T, Seymour ML, Zhang H, et al., 2013. Conditional deletion of Atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of Corti. J. Neurosci, 33(24):10110-10122.
[14]Chen D, Kon N, Li M, et al., 2005. ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor. Cell, 121(7):1071-1083.
[15]Chen P, Johnson JE, Zoghbi HY, et al., 2002. The role of Math1 in inner ear development: uncoupling the establishment of the sensory primordium from hair cell fate determination. Development, 129(10):2495-2505.
[16]Cheng YF, Tong M, Edge ASB, 2016. Destabilization of Atoh1 by E3 ubiquitin ligase Huwe1 and casein kinase 1 is essential for normal sensory hair cell development. J. Biol. Chem, 291(40):21096-21109.
[17]Cox BC, Chai R, Lenoir A, et al., 2014. Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development, 141(4):816-829.
[18]D'Arca D, Zhao X, Xu W, et al., 2010. Huwe1 ubiquitin ligase is essential to synchronize neuronal and glial differentiation in the developing cerebellum. Proc Natl Acad Sci USA, 107(13):5875-5880.
[19]Davis AC, 1983. Hearing disorders in the population: first phase findings of the MRC national study of hearing. In: Lutman ME, Haggard, M.P. (Eds.), Hearing Science and Hearing Disorders. Academic Press Inc. (London) Ltd, London, p.35-60.
[20]Dominguez-Brauer C, Hao Z, Elia AJ, et al., 2016. Mule regulates the intestinal stem cell niche via the Wnt pathway and targets EphB3 for proteasomal and lysosomal degradation. Cell Stem Cell, 19(2):205-216.
[21]Flora A, Garcia J, Thaller C, et al., 2007. The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors. Proc Natl Acad Sci USA, 104(39):15382-15387.
[22]Flora A, Klisch TJ, Schuster G, et al., 2009. Deletion of Atoh1 disrupts sonic hedgehog signaling in the developing cerebellum and prevents medulloblastoma. Science, 326(5958):1424-1427.
[23]Forge A, Li L, Corwin JT, et al., 1993. Ultrastructural evidence for hair cell regeneration in the mammalian inner ear. Science, 259(5101):1616-1619.
[24]Forget A, Bihannic L, Cigna SM, et al., 2014. SHH signaling protects Atoh1 from degradation mediated by the E3 ubiquitin ligase Huwe1 in neural precursors. Dev. Cell, 29(6):649-661.
[25]Fritzsch B, 2003. Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia. Brain Res. Bull, 60(5-6):423-433.
[26]Fröhlich A, Kisielow J, Schmitz I, et al., 2009. IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science, 324(5934):1576-1580.
[27]Gregorieff A, Clevers H, 2005. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev, 19(8):877-890.
[28]Gubbels SP, Woessner DW, Mitchell JC, et al., 2008. Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer. Nature, 455(7212):537-541.
[29]Hall JR, Kow E, Nevis KR, et al., 2007. Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage. Mol. Biol. Cell, 18(9):3340-3350.
[30]Helms AW, Gowan K, Abney A, et al., 2001. Overexpression of MATH1 disrupts the coordination of neural differentiation in cerebellum development. Mol. Cell. Neurosci, 17(4):671-682.
[31]Hu Z, Ulfendahl M, 2006. Cell replacement therapy in the inner ear. Stem Cells Dev, 15(3):449-459.
[32]Hu Z, Andäng M, Ni D, et al., 2005. Neural cograft stimulates the survival and differentiation of embryonic stem cells in the adult mammalian auditory system. Brain Res, 1051(1):137-144.
[33]Huang WH, Tupal S, Huang TW, et al., 2012. Atoh1 governs the migration of postmitotic neurons that shape respiratory effectiveness at birth and chemoresponsiveness in adulthood. Neuron, 75(5):799-809.
[34]Husseman J, Raphael Y, 2009. Gene therapy in the inner ear using adenovirus vectors. In: Ryan, A.F. (Ed.), Gene Therapy of Cochlear Deafness. Advances in Oto-Rhino-Laryngology. Karger, Basel, Vol. 66, p.37-51.
[35]Incesulu A, Nadol JB, 1998. Correlation of acoustic threshold measures and spiral ganglion cell survival in severe to profound sensorineural hearing loss: implications for cochlear implantation. Ann Otol Rhinol Laryngol, 107(11):906-911.
[36]Izumikawa M, Minoda R, Kawamoto K, et al., 2005. Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals. Nat. Med, 11(3):271-276.
[37]Jahan I, Pan N, Kersigo J, et al., 2013. Beyond generalized hair cells: molecular cues for hair cell types. Hear Res, 297:30-41.
[38]Jansson L, Kim GS, Cheng AG, 2015. Making sense of Wnt signaling-linking hair cell regeneration to development. Front. Cell. Neurosci, 9:66.
[39]Jarriault S, Brou C, Logeat F, et al., 1995. Signalling downstream of activated mammalian Notch. Nature, 377(6547):355-358.
[40]Jeon SJ, Fujioka M, Kim SC, et al., 2011. Notch signaling alters sensory or neuronal cell fate specification of inner ear stem cells. J. Neurosci, 31(23):8351-8358.
[41]Kelley MW, 2003. Cell adhesion molecules during inner ear and hair cell development, including notch and its ligands. Curr. Top. Dev. Biol, 57:321-356.
[42]Kelley MW, 2006. Regulation of cell fate in the sensory epithelia of the inner ear. Nat. Rev. Neurosci, 7(11):837-849.
[43]Kurokawa M, Kim J, Geradts J, et al., 2013. A network of substrates of the E3 ubiquitin ligases MDM2 and HUWE1 control apoptosis independently of p53. Sci. Signal, 6(274):ra32.
[44]Lanford PJ, Lan Y, Jiang R, et al., 1999. Notch signalling pathway mediates hair cell development in mammalian cochlea. Nat. Genet, 21(3):289-292.
[45]Li W, Wu J, Yang J, et al., 2015. Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway. Proc Natl Acad Sci USA, 112(1):166-171.
[46]Liu Z, Dearman JA, Cox BC, et al., 2012. Age-dependent in vivo conversion of mouse cochlear pillar and Deiters’ cells to immature hair cells by Atoh1 ectopic expression. J. Neurosci, 32(19):6600-6610.
[47]Liu Z, Fang J, Dearman J, et al., 2014. In vivo generation of immature inner hair cells in neonatal mouse cochleae by ectopic Atoh1 expression. PLoS ONE, 9(2):e89377.
[48]Lo LC, Johnson JE, Wuenschell CW, et al., 1991. Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells. Genes Dev, 5(9):1524-1537.
[49]Maass JC, Gu R, Basch ML, et al., 2015. Changes in the regulation of the Notch signaling pathway are temporally correlated with regenerative failure in the mouse cochlea. Front. Cell. Neurosci, 9:110.
[50]Maksimovic S, Nakatani M, Baba Y, et al., 2014. Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature, 509(7502):617-621.
[51]McLean WJ, Yin X, Lu L, et al., 2017. Clonal expansion of Lgr5-positive cells from mammalian cochlea and high-purity generation of sensory hair cells. Cell Rep, 18(8):1917-1929.
[52]Mianné J, Chessum L, Kumar S, et al., 2016. Correction of the auditory phenotype in C57BL/6N mice via CRISPR/ Cas9-mediated homology directed repair. Genome Med, 8(1):16.
[53]Miesegaes GR, Klisch TJ, Thaller C, et al., 2009. Identification and subclassification of new Atoh1 derived cell populations during mouse spinal cord development. Dev. Biol, 327(2):339-351.
[54]Mizutari K, Fujioka M, Hosoya M, et al., 2013. Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron, 77(1):58-69.
[55]Morrison KM, Miesegaes GR, Lumpkin EA, et al., 2009. Mammalian Merkel cells are descended from the epidermal lineage. Dev. Biol, 336(1):76-83.
[56]Naujokat C, Šarić T, 2007. Concise review: role and function of the ubiquitin-proteasome system in mammalian stem and progenitor cells. Stem Cells, 25(10):2408-2418.
[57]Ni W, Lin C, Guo L, et al., 2016. Extensive supporting cell proliferation and mitotic hair cell generation by in vivo genetic reprogramming in the neonatal mouse cochlea. J. Neurosci, 36(33):8734-8745.
[58]Ohyama T, Mohamed OA, Taketo MM, et al., 2006. Wnt signals mediate a fate decision between otic placode and epidermis. Development, 133(5):865-875.
[59]Pan B, Askew C, Galvin A, et al., 2017. Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. Nat. Biotechnol, 35(3):264-272.
[60]Pan N, Jahan I, Kersigo J, et al., 2012. A novel Atoh1 “self-terminating” mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability. PLoS ONE, 7(1):e30358.
[61]Riccomagno M, Takada S, Epstein D, 2005. Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes Dev, 19(13):1612-1623.
[62]Richardson RT, Atkinson PJ, 2015. Atoh1 gene therapy in the cochlea for hair cell regeneration. Expert Opin Biol Ther, 15(3):417-430.
[63]Rose MF, Ahmad KA, Thaller C, et al., 2009. Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for math1. Proc Natl Acad Sci USA, 106(52):22462-22467.
[64]Ross SE, Greenberg ME, Stiles CD, 2003. Basic helix-loop-helix factors in cortical development. Neuron, 39(1):13-25.
[65]Ruffault PL, D'Autréaux F, Hayes JA, et al., 2015. The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO2. eLife, 4:e07051.
[66]Shi F, Cheng YF, Wang XL, et al., 2010. β-Catenin up-regulates Atoh1 expression in neural progenitor cells by interaction with an Atoh1 3' enhancer. J. Biol. Chem, 285(1):392-400.
[67]Shi F, Kempfle JS, Edge ASB, 2012. Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea. J. Neurosci, 32(28):9639-9648.
[68]Shi F, Hu L, Edge ASB, 2013. Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors. Proc Natl Acad Sci USA, 110(34):13851-13856.
[69]Shi F, Hu L, Jacques BE, et al., 2014. β-Catenin is required for hair-cell differentiation in the cochlea. J. Neurosci, 34(19):6470-6479.
[70]Shroyer NF, Helmrath MA, Wang VYC, et al., 2007. Intestine-specific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology, 132(7):2478-2488.
[71]Shu Y, Tao Y, Wang Z, et al., 2016. Identification of adeno-associated viral vectors that target neonatal and adult mammalian inner ear cell subtypes. Hum. Gene Ther, 27(9):687-699.
[72]Staecker H, Praetorius M, Baker K, et al., 2007. Vestibular hair cell regeneration and restoration of balance function induced by Math1 gene transfer. Otol. Neurotol, 28(2):223-231.
[73]Stevens CB, Davies AL, Battista S, et al., 2003. Forced activation of Wnt signaling alters morphogenesis and sensory organ identity in the chicken inner ear. Dev. Biol, 261(1):149-164.
[74]Tai HC, Schuman EM, 2008. Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nat. Rev. Neurosci, 9(11):826-838.
[75]Takebayashi S, Yamamoto N, Yabe D, et al., 2007. Multiple roles of Notch signaling in cochlear development. Dev. Biol, 307(1):165-178.
[76]Tiveron MC, Pattyn A, Hirsch MR, et al., 2003. Role of Phox2b and Mash1 in the generation of the vestibular efferent nucleus. Dev. Biol, 260(1):46-57.
[77]Tsuchiya K, Nakamura T, Okamoto R, et al., 2007. Reciprocal targeting of Hath1 and β-catenin by Wnt glycogen synthase kinase 3β in human colon cancer. Gastroenterology, 132(1):208-220.
[78]Urbán N, van den Berg DLC, Forget A, et al., 2016. Return to quiescence of mouse neural stem cells by degradation of a proactivation protein. Science, 353(6296):292-295.
[79]VanDussen KL, Samuelson LC, 2010. Mouse atonal homolog 1 directs intestinal progenitors to secretory cell rather than absorptive cell fate. Dev. Biol, 346(2):215-223.
[80]van Keymeulen A, Mascre G, Youseff KK, et al., 2009. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J. Cell Biol, 187(1):91-100.
[81]Varshavsky A, 1991. Naming a targeting signal. Cell, 64(1):13-15.
[82]Wang T, Chai R, Kim GS, et al., 2015. Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle. Nat. Commun, 6:6613.
[83]Wang VY, Rose MF, Zoghbi HY, 2005. Math1 expression redefines the rhombic lip derivatives and reveals novel lineages within the brainstem and cerebellum. Neuron, 48(1):31-43.
[84]Warchol ME, Lambert PR, Goldstein BJ, et al., 1993. Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans. Science, 259(5101):1619-1623.
[85]WHO (World Health Organization), 2017. Deafness and hearing loss. Fact sheet, WHO Media Centre.
[86]Woods C, Montcouquiol M, Kelley MW, 2004. Math1 regulates development of the sensory epithelium in the mammalian cochlea. Nat. Neurosci, 7(12):1310-1318.
[87]Wright MC, Reed-Geaghan EG, Bolock AM, et al., 2015. Unipotent, Atoh1+ progenitors maintain the Merkel cell population in embryonic and adult mice. J. Cell Biol, 208(3):367-379.
[88]Yamamoto N, Tanigaki K, Tsuji M, et al., 2006. Inhibition of Notch/RBP-J signaling induces hair cell formation in neonate mouse cochleas. J. Mol. Med, 84(1):37-45.
[89]Yang H, Xie X, Deng M, et al., 2010. Generation and characterization of Atoh1-Cre knock-in mouse line. Genesis, 48(6):407-413.
[90]Yang Q, Bermingham NA, Finegold MJ, et al., 2001. Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science, 294(5549):2155-2158.
[91]Zhao H, Ayrault O, Zindy F, et al., 2008. Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development. Genes Dev, 22(6):722-727.
[92]Zhao X, Heng JIT, Guardavaccaro D, et al., 2008. The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein. Nat. Cell Biol, 10(6):643-653.
[93]Zhao X, D'Arca D, Lim WK, et al., 2009. The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain. Dev. Cell, 17(2):210-221.
[94]Zheng JL, Gao WQ, 2000. Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears. Nat. Neurosci, 3(6):580-586.
[95]Zou B, Mittal R, Grati M, et al., 2015. The application of genome editing in studying hearing loss. Hear. Res, 327:102-108.
[96]Zuris JA, Thompson DB, Shu Y, et al., 2015. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat. Biotechnol, 33(1):73-80.
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