Wnt信号通路在毛细胞分化和再生过程中的作用

doi:10.16288/j.yczz.17-037

遗传 ›› 2017, Vol. 39 ›› Issue (10): 897-907.doi: 10.16288/j.yczz.17-037

Wnt信号通路在毛细胞分化和再生过程中的作用

范晴晴(),孟飞龙,房冉,李高鹏,赵小立()

浙江大学生命科学学院遗传与再生生物学研究所,浙江省细胞与基因工程重点研究实验室,杭州 310058

收稿日期:2017-02-08 修回日期:2017-04-03 出版日期:2017-10-20 发布日期:2017-09-19
作者简介:范晴晴,硕士研究生,专业方向：干细胞分化。E-mail: 21407051@zju.edu.cn|赵小立，副教授，硕士生导师，研究方向：干细胞分化。E-mail: zhaoxiaoli@zju.edu.cn
基金资助:
国家重点基础研究发展规划(973计划)(2012CB967900)

Functions of Wnt signaling pathway in hair cell differentiation and regeneration

Fan Qingqing(),Meng Feilong,Fang Ran,Li Gaopeng,Zhao Xiaoli()

Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Institute of Genetics and Regenerative Biology, College of Life Sciences, Zhejiang University, Hangzhou 310058, China

Received:2017-02-08 Revised:2017-04-03 Online:2017-10-20 Published:2017-09-19
Supported by:
the National Program on Key Basic Research Project (973 Program)(2012CB967900)

摘要/Abstract

摘要：

Wnt信号通路在生物发育和维持内环境稳态过程中起着重要作用。Wnt配体通过与Frizzle受体结合参与体轴的形成、细胞分化和细胞命运决定等生命活动。在小鼠内耳发育过程中,Wnt信号通路扮演了重要角色：在内耳发育早期阶段,参与听基板的特化和听泡的形成;在内耳发育后期阶段,调控毛细胞分化及毛细胞纤毛束的定向。本文综述了Wnt信号通路在内耳毛细胞发育分化及再生过程中的研究进展,以期为从事相关领域的科研人员提供参考。

关键词: Wnt信号通路, 听基板, 听泡, 毛细胞再生

Abstract:

Wnt signaling pathway plays important roles in the development and homeostasis of multicellular organisms. Through their bindings with the Frizzled receptors, the Wnt ligands regulate a wide range of developmental processes, such as axis patterning, cell division, and cell fate specification. Wnt signaling plays vital roles in the development of inner ear of the mouse. In the early stages of inner ear development, Wnt signaling specifies the size of the placode and the formation of the otic vesicle. In later stages, Wnt signaling mediates hair cell specification and orients the stereociliary bundles in a uniform direction. In this review, we summarize the current knowledge on the roles of Wnt signaling in hair cell differentiation and regeneration, which may provide references and insights for investigators in the field.

Key words: Wnt signaling pathway, otic placode, otic vesicle, hair cell regeneration

范晴晴, 孟飞龙, 房冉, 李高鹏, 赵小立. Wnt信号通路在毛细胞分化和再生过程中的作用[J]. 遗传, 2017, 39(10): 897-907.

Fan Qingqing, Meng Feilong, Fang Ran, Li Gaopeng, Zhao Xiaoli. Functions of Wnt signaling pathway in hair cell differentiation and regeneration[J]. Hereditas(Beijing), 2017, 39(10): 897-907.

参考文献

[1]	Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol, 2004, 20: 781-810.
[2]	Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol, 1998, 14(1): 59-88.
[3]	van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development. Development, 2009, 136(19): 3205-3214.
[4]	Flaherty MP, Dawn B. Noncanonical Wnt11 signaling and cardiomyogenic differentiation. Trends Cardiovasc Med, 2008, 18(7): 260-268.
[5]	Nelson WJ, Nusse R. Convergence of Wnt, β-catenin, and cadherin pathways. Science, 2004, 303(5663): 1483-1487.
[6]	Petersen CP, Reddien PW. Wnt signaling and the polarity of the primary body axis. Cell, 2009, 139(6): 1056-1068.
[7]	Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem, 2006, 281(32): 22429-22433.
[8]	Munnamalai V, Fekete DM. Wnt signaling during cochlear development. Semin Cell Dev Biol, 2013, 24(5): 480-489.
[9]	Gómez-Orte E, Sáenz-Narciso B, Moreno S, Cabello J. Multiple functions of the noncanonical Wnt pathway. Trends Genet, 2013, 29(9): 545-553.
[10]	Geng RH, Noda T, Mulvaney JF, Lin VYW, Edge ASB, Dabdoub A. Comprehensive expression of Wnt signaling pathway genes during development and maturation of the mouse cochlea. PLoS One, 2016, 11(2): e0148339.
[11]	Barald KF, Kelley MW. From placode to polarization: new tunes in inner ear development. Development, 2004, 131(17): 4119-4130.
[12]	Fritzsch B, Pan N, Jahan I, Elliott KL. Inner ear development: building a spiral ganglion and an organ of Corti out of unspecified ectoderm. Cell Tissue Res, 2015, 361(1): 7-24.
[13]	Zhang YP, Chen Y, Ni WL, Guo L, Lu XL, Liu LM, Li W, Sun S, Wang L, Li HW. Dynamic expression of Lgr6 in the developing and mature mouse cochlea. Front Cell Neurosci, 2015, 9: 165.
[14]	Pirvola U, Ylikoski J, Trokovic R, Hébert JM, McConnell SK, Partanen J. FGFR1 is required for thedevelopment of the auditory sensory epithelium. Neuron, 2002, 35(4): 671-680.
[15]	Pan W, Jin Y, Stangerc B, Kiernan AE. Notch signaling is required for the generation of hair cells and supporting cells in the mammalian inner ear. Proc Natl Acad Sci USA, 2010, 107(36): 15798-15803.
[16]	Kiernan AE, Xu J, Gridley T. The Notch ligand JAG1 is required for sensory progenitor development in the mammalian inner ear. PLoS Genet, 2006, 2(1): e4.
[17]	Ono K, Kita T, Sato S, O'Neill P, Mak SS, Paschaki M, Ito M, Gotoh N, Kawakami K, Sasai Y, Ladher RK. FGFR1- Frs2/3 signalling maintains sensory progenitors during inner ear hair cell formation. PLoS Genet, 2014, 10(1): e1004118.
[18]	Ohyama T, Basch ML, Mishina Y, Lyons KM, Segil N, Groves AK. BMP signaling is necessary for patterning the sensory and nonsensory regions of the developing mammalian cochlea. J Neurosci, 2010, 30(45): 15044-15051.
[19]	Camarero G, Avendano C, Fernández-Moreno C, Villar A, Contreras J, de Pablo F, Pichel JG, Varela-Nieto I. Delayed inner ear maturation and neuronal loss in postnatal Igf-1-deficient mice. J Neurosci, 2001, 21(19): 7630-7641.
[20]	Brown AS, Rakowiecki SM, Li JYH, Epstein DJ. The cochlear sensory epithelium derives from Wnt responsive cells in the dorsomedial otic cup. Dev Biol, 2015, 399(1): 177-187.
[21]	Ladher RK, Wright TJ, Moon AM, Mansour SL, Schoenwolf GC. FGF8 initiates inner ear induction in chick and mouse. Genes Dev, 2005, 19(5): 603-613.
[22]	Wright TJ, Mansour SL. Fgf3 and Fgf10 are required for mouse otic placode induction. Development, 2003, 130(15): 3379-3390.
[23]	Lleras-Forero L, Streit A. Development of the sensory nervous system in the vertebrate head: the importance of being on time. Curr Opin Genet Dev, 2012, 22(4): 315-322.
[24]	Groves AK, Fekete DM. Shaping sound in space: the regulation of inner ear patterning. Development, 2012, 139(2): 245-257.
[25]	Chen JC, Streit A. Induction of the inner ear: stepwise specification of otic fate from multipotent progenitors. Hear Res, 2013, 297: 3-12.
[26]	Wright KD, Mahoney Rogers AA, Zhang J, Shim K. Cooperative and independent functions of FGF and Wnt signaling during early inner ear development. BMC Dev Biol, 2015, 15: 33.
[27]	Groves AK, LaBonne C. Setting appropriate boundaries: fate, patterning and competence at the neural plate border. Dev Biol, 2014, 389(1): 2-12.
[28]	Koehler KR, Mikosz AM, Molosh AI, Patel D, Hashino E. Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature, 2013, 500(7461): 217-221.
[29]	Li WY, Wu JF, Yang JM, Suna S, Chai RJ, Chen ZY, Li HW. Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway. Proc Natl Acad Sci USA, 2014, 112(1): 166-171.
[30]	Chai RJ, Kuo B, Wang T, Liaw EJ, Xia AP, Jan TA, Liu ZY, Taketo MM, Oghalai JS, Nusse R, Zuo J, Cheng AG. Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc Natl Acad Sci USA, 2012, 109(21): 8167-8172.
[31]	Ohyama T, Mohamed OA, Taketo MM, Dufort D, Groves AK. Wnt signals mediate a fate decision between otic placode and epidermis. Development, 2006, 133(5): 865-875.
[32]	Waqas M, Zhang SS, He ZH, Tang ML, Chai RJ. Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea. Front Med, 2016, 10(3): 237-249.
[33]	Lin ZS, Cantos R, Patente M, Wu DK. Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling. Development, 2005, 132(10): 2309-2318.
[34]	Robledo RF, Lufkin T. Dlx5 and Dlx6 homeobox genes are required for specification of the mammalian vestibular apparatus. Genesis, 2006, 44(9): 425-437.
[35]	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(13): 1612-1623.
[36]	Chen ZQ, Han XH, Cao X. Sonic Hedgehog signaling pathway and regulation of inner ear development. Hereditas (Beijing), 2013, 35(9): 1058-1064.
[36]	陈志强, 韩新焕, 曹新. Sonic Hedgehog信号通路与内耳发育调控. 遗传, 2013, 35(9): 1058-1064.
[37]	Kelley MW. Regulation of cell fate in the sensory epithelia of the inner ear. Nat Rev Neurosci, 2006, 7(11): 837-849.
[38]	Nayagam BA, Muniak MA, Ryugo DK. The spiral ganglion: connecting the peripheral and central auditory systems. Hear Res, 2011, 278(1-2): 2-20.
[39]	Hudspeth AJ. Integrating the active process of hair cells with cochlear function. Nat Rev Neurosci, 2014, 15(9): 600-614.
[40]	Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell, 2005, 122(6): 947-956.
[41]	Dabdoub A, Puligilla C, Jones JM, Fritzsch B, Cheah KSE, Pevny LH, Kelley MW. Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea. Proc Natl Acad Sci USA, 2008, 105(47): 18396-18401.
[42]	Kempfle JS, Turban JL, Edge ASB. Sox2 in the differentiation of cochlear progenitor cells. Sci Rep, 2016, 6: 23293.
[43]	Jacques BE, Puligilla C, Weichert RM, Ferrer-Vaquer A, Hadjantonakis AK, Kelley MW, Dabdoub A. A dual function for canonical Wnt/β-catenin signaling in the developing mammalian cochlea. Development, 2012, 139(23): 4395-4404.
[44]	MacDonald BT, Tamai K, He X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell, 2009, 17(1): 9-26.
[45]	Handeli S, Simon JA. A small-molecule inhibitor of Tcf/β-catenin signaling down-regulates PPARγ and PPARδ activities. Mol Cancer Ther, 2008, 7(3): 521-529.
[46]	Klein PS, Melton DA. A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci USA, 1996, 93(16): 8455-8459.
[47]	Jin YR, Yoon JK. The R-spondin family of proteins: emerging regulators of WNT signaling. Int J Biochem Cell Biol, 2012, 44(12): 2278-2287.
[48]	de Lau WB, Snel B, Clevers HC. The R-spondin protein family. Genome Biol, 2012, 13(3): 242-252.
[49]	deLau W, Barker N, Low TY, Koo BK, Li VSW, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M, Stange DE, van Es J, Guardavaccaro D, Schasfoort RBM, Mohri Y, Nishimori K, Mohammed S, Heck AJR, Clevers H. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature, 2011, 476(7360): 293-297.
[50]	Mulvaney JF, Yatteau A, Sun WW, Jacques B, Takubo K, Suda T, Yamada W, Dabdoub A. Secreted factor R-Spondin 2 is involved in refinement of patterning of the mammalian cochlea. Dev Dyn, 2013, 242(2): 179-188.
[51]	Schuijers J, Clevers H. Adult mammalian stem cells: the role of Wnt, Lgr5 and R-spondins. EMBO J, 2012, 31(12): 2685-2696.
[52]	Klein TJ, Mlodzik M. Planar cell polarization: an emerging model points in the right direction. Annu Rev Cell Dev Biol, 2005, 21: 155-176.
[53]	Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, Ingelfinger D, Boutros M, Cruciat CM, Niehrs C. LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling. EMBO Rep, 2011, 12(10): 1055-1061.
[54]	Dabdoub A, Donohue MJ, Brennan A, Wolf V, Montcouquiol M, Sassoon DA, Hseih JC, Rubin JS, Salinas PC, Kelley MW. Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea. Development, 2003, 130(11): 2375-2384.
[55]	Qian D, Jones C, Rzadzinska A, Mark S, Zhang XH, Steel KP, Dai X, Chen P. Wnt5a functions in planar cell polarity regulation in mice. Dev Biol, 2007, 306(1): 121-133.
[56]	Furness DN. Molecular basis of hair cell loss. Cell Tissue Res, 2015, 361(1): 387-399.
[57]	Rubel EW, Furrer SA, Stone JS. A brief history of hair cell regeneration research and speculations on the future. Hear Res, 2013, 297: 42-51.
[58]	Jansson L, Kim GS, Cheng AG. Making sense of Wnt signaling-linking hair cell regeneration to development. Front Cell Neurosci, 2015, 9: 66.
[59]	Wu JF, Li WY, Lin C, Chen Y, Cheng C, Sun S, Tang ML, Chai RJ, Li HW. Co-regulation of the Notch and Wnt signaling pathways promotes supporting cell proliferation and hair cell regeneration in mouse utricles. Sci Rep, 2016, 6: 29418.
[60]	Head JR, Gacioch L, Pennisi M, Meyers JR. Activation of canonical Wnt/β-catenin signaling stimulates proliferation in neuromasts in the zebrafish posterior lateral line. Dev Dyn, 2013, 242(7): 832-846.
[61]	Yin A, Korzh S, Winata CL, Korzh V, Gong ZY. Wnt signaling is required for early development of zebrafish swimbladder. PLoS One, 2011, 6(3): e18431.
[62]	Alvarado DM, Hawkins RD, Bashiardes S, Veile RA, Ku YC, Powder KE, Spriggs MK, Speck JD, Warchol ME, Lovett M. An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear. J Neurosci, 2011, 31(12): 4535-4543.
[63]	Jacques BE, Montgomery IV WHM, Uribe PM, Yatteau A, Asuncion JD, Resendiz G, Matsui JI, Dabdoub A. The role of Wnt/β-catenin signaling in proliferation and regeneration of the developing basilar papilla and lateral line. Dev Neurobiol, 2014, 74(4): 438-456.
[64]	Shi FX, Hu LX, Edge ASB. Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors. Proc Natl Acad Sci USA, 2013, 110(34): 13851-13856.
[65]	Chai RJ, Xia AP, Wang T, Jan TA, Hayashi T, Bermingham-McDonogh O, Cheng AGL. Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea. J Assoc Res Otolaryngol, 2011, 12(4): 455-469.
[66]	Shi FX, Hu LX, Jacques BE, Mulvaney JF, Dabdoub A, Edge ASB. β-Catenin is required for hair-cell differentiation in the cochlea. J Neurosci, 2014, 34(19): 6470-6479.
[67]	Liu ZY, Fang J, Dearman J, Zhang LL, Zuo J. In vivo generation of immature inner hair cells in neonatal mouse cochleae by ectopic Atoh1 expression. PLoS One, 2014, 9(2): e89377.
[68]	Kawamoto K, Ishimoto SI, Minoda R, Brough DE, Raphael Y. Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo. J Neurosci, 2003, 23(11): 4395-4400.
[69]	Kuo BR, Baldwin EM, Layman WS, Taketo MM, Zuo J. In vivo cochlear hair cell generation and survival by coactivation of β-catenin and atoh1. J Neurosci, 2015, 35(30): 10786-10798.

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Wnt信号通路在毛细胞分化和再生过程中的作用

Functions of Wnt signaling pathway in hair cell differentiation and regeneration

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