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Cell and Tissue Research

, Volume 370, Issue 1, pp 89–97 | Cite as

Spatiotemporal expression patterns of clusterin in the mouse inner ear

  • Seokwon Lee
  • Jeong-Oh Shin
  • Borum Sagong
  • Un-Kyung KimEmail author
  • Jinwoong BokEmail author
Regular Article
  • 459 Downloads

Abstract

Clusterin (CLU) is an extracellular chaperone protein that is implicated in diverse physiological and pathophysiological cellular processes. CLU expression is upregulated in response to cellular stress and under certain conditions, such as neurodegenerative disease and cancer. CLU primarily functions as a chaperone that exerts cytoprotective effects by removing cellular debris and misfolded proteins and also acts as a signaling molecule that regulates pro-survival pathways. Deafness is caused by genetic factors and various extrinsic insults, including ototoxic drugs, exposure to loud sounds and aging. Considering its cytoprotectivity, CLU may also mediate cellular defense mechanisms against hearing loss due to cellular stresses. To understand the function of CLU in the inner ear, we analyze CLU expression patterns in the mouse inner ear during development and in the adult stage. Results of quantitative real-time polymerase chain reaction analysis showed that Clu mRNA levels in the inner ear were increased during embryogenesis and were constantly expressed in the adult. Detailed spatial expression patterns of Clu both in the mRNA and protein levels were analyzed throughout various developmental stages via in situ hybridization and immunofluorescence staining. Clu expression was found in specific domains of developing inner ear starting from the otocyst stage, mainly adjacent to the prosensory domain of the cochlear epithelium. In the mature inner ear, Clu expression was observed in Deiter’s cells and pillar cells of the organ of Corti, outer sulcus and in basal cells of the stria vascularis in the cochlea. These specific spatiotemporal expression patterns suggest the possible roles of CLU in inner ear development and in maintaining proper hearing function.

Keywords

Clusterin Inner ear Expression Spatiotemporal Mouse 

Notes

Acknowledgements

This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea, funded by the Ministry of Science, Information and Communications Technology and Future Planning (2014M3A9D5073865 to J.B. and U.K.K. and 2016R1A5A2008630 to J.B.) and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C0384 to J.B.).

References

  1. Bok J, Chang W, Wu DK (2007) Patterning and morphogenesis of the vertebrate inner ear. Int J Dev Biol 51:521–533CrossRefPubMedGoogle Scholar
  2. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55:611–622CrossRefPubMedGoogle Scholar
  3. Charnay Y, Imhof A, Vallet PG, Hakkoum D, Lathuiliere A, Poku N, Aronow B, Kovari E, Bouras C, Giannakopoulos P (2008) Clusterin expression during fetal and postnatal CNS development in mouse. Neuroscience 155:714–724CrossRefPubMedGoogle Scholar
  4. Colvin JS, Bohne BA, Harding GW, McEwen DG, Ornitz DM (1996) Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. Nat Genet 12:390–397CrossRefPubMedGoogle Scholar
  5. Dvorakova M, Jahan I, Macova I, Chumak T, Bohuslavova R, Syka J, Fritzsch B, Pavlinkova G (2016) Incomplete and delayed Sox2 deletion defines residual ear neurosensory development and maintenance. Sci Rep 6:38253CrossRefPubMedPubMedCentralGoogle Scholar
  6. Groves AK, Fekete DM (2012) Shaping sound in space: the regulation of inner ear patterning. Development 139:245–257CrossRefPubMedPubMedCentralGoogle Scholar
  7. Helms AW, Johnson JE (1998) Progenitors of dorsal commissural interneurons are defined by MATH1 expression. Development 125:919–928PubMedGoogle Scholar
  8. Jahan I, Pan N, Fritzsch B (2015) 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 9:26CrossRefPubMedPubMedCentralGoogle Scholar
  9. Kiernan AE, Pelling AL, Leung KK, Tang AS, Bell DM, Tease C, Lovell-Badge R, Steel KP, Cheah KS (2005) Sox2 is required for sensory organ development in the mammalian inner ear. Nature 434:1031–1035CrossRefPubMedGoogle Scholar
  10. Kopecky BJ, Jahan I, Fritzsch B (2013) Correct timing of proliferation and differentiation is necessary for normal inner ear development and auditory hair cell viability. Dev Dyn 242:132–147CrossRefPubMedPubMedCentralGoogle Scholar
  11. Leeb C, Eresheim C, Nimpf J (2014) Clusterin is a ligand for apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) and signals via the Reelin-signaling pathway. J Biol Chem 289:4161–4172CrossRefPubMedGoogle Scholar
  12. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408CrossRefPubMedGoogle Scholar
  13. Mellado Lagarde MM, Cox BC, Fang J, Taylor R, Forge A, Zuo J (2013) Selective ablation of pillar and deiters’ cells severely affects cochlear postnatal development and hearing in mice. J Neurosci 33:1564–1576CrossRefPubMedGoogle Scholar
  14. Morsli H, Choo D, Ryan A, Johnson R, Wu DK (1998) Development of the mouse inner ear and origin of its sensory organs. J Neurosci 18:3327–3335PubMedGoogle Scholar
  15. Pauley S, Lai E, Fritzsch B (2006) Foxg1 is required for morphogenesis and histogenesis of the mammalian inner ear. Dev Dyn 235:2470–2482CrossRefPubMedPubMedCentralGoogle Scholar
  16. Poirrier AL, Pincemail J, Van Den Ackerveken P, Lefebvre PP, Malgrange B (2010) Oxidative stress in the cochlea: an update. Curr Med Chem 17:3591–3604CrossRefPubMedGoogle Scholar
  17. Raft S, Nowotschin S, Liao J, Morrow BE (2004) Suppression of neural fate and control of inner ear morphogenesis by Tbx1. Development 131:1801–1812CrossRefPubMedGoogle Scholar
  18. Rohne P, Prochnow H, Koch-Brandt C (2016) The CLU-files: disentanglement of a mystery. Biomol Concepts 7:1–15CrossRefPubMedGoogle Scholar
  19. Song MH, Choi SY, Wu L, Oh SK, Lee HK, Lee DJ, Shim DB, Choi JY, Kim UK, Bok J (2011) Pou3f4 deficiency causes defects in otic fibrocytes and stria vascularis by different mechanisms. Biochem Biophys Res Commun 404:528–533CrossRefPubMedGoogle Scholar
  20. Stucken EZ, Hong RS (2014) Noise-induced hearing loss: an occupational medicine perspective. Curr Opin Otolaryngol Head Neck Surg 22:388–393CrossRefPubMedGoogle Scholar
  21. Trougakos IP (2013) The molecular chaperone apolipoprotein J/clusterin as a sensor of oxidative stress: implications in therapeutic approaches - a mini-review. Gerontology 59:514–523CrossRefPubMedGoogle Scholar
  22. Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, Casey DC, Charlson FJ, Chen AZ, Coggeshall M, Cornaby L, Dandona L, Dicker DJ, Dilegge T, Erskine HE, Ferrari AJ, Fitzmaurice C, Fleming T, Forouzanfar MH, Fullman N, Gething PW, Goldberg EM, Graetz N, Haagsma JA, Johnson CO, Kassebaum NJ, Kawashima T, Kemmer L, Khalil IA, Kinfu Y, Kyu HH, Leung J, Liang X, Lim SS, Lopez AD, Lozano R, Marczak L, Mensah GA, Mokdad AH, Naghavi M, Nguyen G, Nsoesie E, Olsen H, Pigott DM, Pinho C, Rankin Z, Reinig N, Salomon JA, Sandar L, Smith A, Stanaway J, Steiner C, Teeple S, Thomas BA, Troeger C, Wagner JA, Wang H, Wanga V, Whiteford HA, Zoeckler L, Abajobir AA, Abate KH, Abbafati C, Abbas KM, Abd-Allah F, Abraham B, Abubakar I, Abu-Raddad LJ, Abu-Rmeileh NME, Ackerman IN, Adebiyi AO, Ademi Z, Adou AK, Afanvi KA, Agardh EE, Agarwal A, Kiadaliri AA, Ahmadieh H, Ajala ON, Akinyemi RO, Akseer N, Al-Aly Z, Alam K, Alam NKM, Aldhahri SF, Alegretti MA, Alemu ZA, Alexander LT, Alhabib S, Ali R, Aa A, Alla F, Allebeck P, Al-Raddadi R, Alsharif U, Altirkawi KA, Alvis-Guzman N, Amare AT, Amberbir A, Amini H, Ammar W, Amrock SM, Andersen HH, Anderson GM, Anderson BO, Antonio CAT, Aregay AF, Ärnlöv J, Artaman A, Asayesh H, Assadi R, Atique S, Avokpaho EFGA, Awasthi A, Quintanilla BPA, Azzopardi P, Bacha U, Badawi A, Balakrishnan K, Banerjee A, Barac A, Barker-Collo SL, Bärnighausen T, Barregard L, Barrero LH, Basu A, Bazargan-Hejazi S, Bell B, Bell ML, Bennett DA, Bensenor IM, Benzian H, Berhane A, Bernabé E, Betsu BD, Beyene AS, Bhala N, Bhatt S, Biadgilign S, Bienhoff K, Bikbov B, Biryukov S, Bisanzio D, Bjertness E, Blore J, Borschmann R, Sa B, Brainin M, Brazinova A, Breitborde NJK, Brown J, Buchbinder R, Buckle GC, Butt ZA, Calabria B, Campos-Nonato IR, Campuzano JC, Carabin H, Cárdenas R, Carpenter DO, Carrero JJ, Castañeda-Orjuela CA, Rivas JC, Catalá-López F, Chang J-C, Chiang PP-C, Chibueze CE, Chisumpa VH, Choi J-YJ, Chowdhury R, Christensen H, Christopher DJ, Ciobanu LG, Cirillo M, Coates MM, Colquhoun SM, Cooper C, Cortinovis M, Crump JA, Damtew SA, Dandona R, Daoud F, Dargan PI, Jd N, Davey G, Davis AC, Leo DD, Degenhardt L, Gobbo LCD, Dellavalle RP, Deribe K, Deribew A, Derrett S, Jarlais DCD, Dharmaratne SD, Dhillon PK, Diaz-Torné C, Ding EL, Driscoll TR, Duan L, Dubey M, Duncan BB, Ebrahimi H, Ellenbogen RG, Elyazar I, Endres M, Endries AY, Ermakov SP, Eshrati B, Estep K, Farid TA, CSaeS F, Faro A, Farvid MS, Farzadfar F, Feigin VL, Felson DT, Fereshtehnejad S-M, Fernandes JG, Fernandes JC, Fischer F, JRA F, Foreman K, FGR F, Fox J, Franklin RC, Friedman J, Frostad J, Fürst T, Futran ND, Gabbe B, Ganguly P, Gankpé FG, Gebre T, Gebrehiwot TT, Gebremedhin AT, Geleijnse JM, Gessner BD, Gibney KB, IAM G, Giref AZ, Giroud M, Gishu MD, Glaser E, Godwin WW, Gomez-Dantes H, Gona P, Goodridge A, Gopalani SV, Gotay CC, Goto A, Gouda HN, Grainger R, Greaves F, Guillemin F, Guo Y, Gupta R, Gupta R, Gupta V, Gutiérrez RA, Haile D, Hailu AD, Hailu GB, Halasa YA, Hamadeh RR, Hamidi S, Hammami M, Hancock J, Handal AJ, Hankey GJ, Hao Y, Harb HL, Harikrishnan S, Haro JM, Havmoeller R, Hay RJ, Heredia-Pi IB, Heydarpour P, Hoek HW, Horino M, Horita N, Hosgood HD, Hoy DG, Htet AS, Huang H, Huang JJ, Huynh C, Iannarone M, Iburg KM, Innos K, Inoue M, Iyer VJ, Jacobsen KH, Jahanmehr N, Jakovljevic MB, Javanbakht M, Jayatilleke AU, Jee SH, Jeemon P, Jensen PN, Jiang Y, Jibat T, Jimenez-Corona A, Jin Y, Jonas JB, Kabir Z, Kalkonde Y, Kamal R, Kan H, Karch A, Karema CK, Karimkhani C, Kasaeian A, Kaul A, Kawakami N, Keiyoro PN, Kemp AH, Keren A, Kesavachandran CN, Khader YS, Khan AR, Khan EA, Khang Y-H, Khera S, TkAM K, Khubchandani J, Kieling C, Kim P, Kim C-i, Kim D, Kim YJ, Kissoon N, Knibbs LD, Knudsen AK, Kokubo Y, Kolte D, Kopec JA, Kosen S, Kotsakis GA, Koul PA, Koyanagi A, Kravchenko M, Defo BK, Bicer BK, Kudom AA, Kuipers EJ, Kumar GA, Kutz M, Kwan GF, Lal A, Lalloo R, Lallukka T, Lam H, Lam JO, Langan SM, Larsson A, Lavados PM, Leasher JL, Leigh J, Leung R, Levi M, Li Y, Li Y, Liang J, Liu S, Liu Y, Lloyd BK, Lo WD, Logroscino G, Looker KJ, Lotufo PA, Lunevicius R, Lyons RA, Mackay MT, MMAE R, Mahdavi M, Majdan M, Majeed A, Malekzadeh R, Marcenes W, Margolis DJ, Martinez-Raga J, Masiye F, Massano J, McGarvey ST, McGrath JJ, McKee M, McMahon BJ, Meaney PA, Mehari A, Mejia-Rodriguez F, Mekonnen AB, Melaku YA, Memiah P, Memish ZA, Mendoza W, Meretoja A, Meretoja TJ, Mhimbira FA, Miller TR, Mills EJ, MM n, Mitchell PB, Mock CN, Mohammadi A, Su M, Monasta L, JCM H, Montico M, Mooney MD, Moradi-Lakeh M, Morawska L, Mueller UO, Mullany E, Mumford JE, Murdoch ME, Nachega JB, Nagel G, Naheed A, Naldi L, Nangia V, Newton JN, Ng M, Ngalesoni FN, Nguyen QL, Nisar MI, PMN P, Nolla JM, Norheim OF, Norman RE, Norrving B, Nunes BP, Ogbo FA, Oh I-H, Ohkubo T, Olivares PR, Olusanya BO, Olusanya JO, Ortiz A, Osman M, Ota E, PA M, Park E-K, Parsaeian M, VMdA P, AJP C, Patten SB, Patton GC, Pereira DM, Perez-Padilla R, Perico N, Pesudovs K, Petzold M, Phillips MR, Piel FB, Pillay JD, Pishgar F, Plass D, Platts-Mills JA, Polinder S, Pond CD, Popova S, Poulton RG, Pourmalek F, Prabhakaran D, Prasad NM, Qorbani M, RHS R, Radfar A, Rafay A, Rahimi K, Rahimi-Movaghar V, Rahman M, MHU R, Rahman SU, Rai RK, Rajsic S, Ram U, Rao P, Refaat AH, Reitsma MB, Remuzzi G, Resnikoff S, Reynolds A, Ribeiro AL, MJR B, Roba HS, Rojas-Rueda D, Ronfani L, Roshandel G, Roth GA, Rothenbacher D, Roy A, Sagar R, Sahathevan R, Sanabria JR, Sanchez-Niño MD, Santos IS, Santos JV, Sarmiento-Suarez R, Sartorius B, Satpathy M, Savic M, Sawhney M, Schaub MP, Schmidt MI, IJC S, Schöttker B, Schwebel DC, Scott JG, Seedat S, Sepanlou SG, Servan-Mori EE, Shackelford KA, Shaheen A, Shaikh MA, Sharma R, Sharma U, Shen J, Shepard DS, Sheth KN, Shibuya K, Shin M-J, Shiri R, Shiue I, Shrime MG, Sigfusdottir ID, DAS S, DGA S, Singh A, Singh JA, Singh OP, Singh PK, Sivonda A, Skirbekk V, JCe S, Sligar A, Sliwa K, Soljak M, Søreide K, Soriano JB, Sposato LA, Sreeramareddy CT, Stathopoulou V, Steel N, Stein DJ, Steiner TJ, Steinke S, Stovner L, Stroumpoulis K, Sunguya BF, Sur P, Swaminathan S, Sykes BL, CEI S, Tabarés-Seisdedos R, Takala JS, Tandon N, Tanne D, Tavakkoli M, Taye B, Taylor HR, BJT A, Tedla BA, Terkawi AS, Thomson AJ, Thorne-Lyman AL, Thrift AG, Thurston GD, Tobe-Gai R, Tonelli M, Topor-Madry R, Topouzis F, Tran BX, Dimbuene ZT, Tsilimbaris M, Tura AK, Tuzcu EM, Tyrovolas S, Ukwaja KN, Undurraga EA, Uneke CJ, Uthman OA, CHv G, Varakin YY, Vasankari T, Venketasubramanian N, Verma RK, Violante FS, Vladimirov SK, Vlassov VV, Vollset SE, Wagner GR, Waller SG, Wang L, Watkins DA, Weichenthal S, Weiderpass E, Weintraub RG, Werdecker A, Westerman R, White RA, Williams HC, Wiysonge CS, CDA W, Won S, Woodbrook R, Wubshet M, Xavier D, Xu G, Yadav AK, Yan LL, Yano Y, Yaseri M, Ye P, Yebyo HG, Yip P, Yonemoto N, Yoon S-J, Younis MZ, Yu C, Zaidi Z, MES Z, Zeeb H, Zhou M, Zodpey S, Zuhlke LJ, CJL M (2016) Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the global burden of disease study 2015. Lancet 388:1545–1602CrossRefGoogle Scholar
  23. Yoon H, Lee DJ, Kim MH, Bok J (2011) Identification of genes concordantly expressed with Atoh1 during inner ear development. Anat Cell Biol 44:69–78CrossRefPubMedPubMedCentralGoogle Scholar
  24. Zhang F, Kumano M, Beraldi E, Fazli L, Du C, Moore S, Sorensen P, Zoubeidi A, Gleave ME (2014) Clusterin facilitates stress-induced lipidation of LC3 and autophagosome biogenesis to enhance cancer cell survival. Nat Commun 5:5775CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Biology, College of Natural SciencesKyungpook National UniversityDaeguRepublic of Korea
  2. 2.School of Life Sciences, BK21 Plus KNU Creative BioResearch GroupKyungpook National UniversityDaeguRepublic of Korea
  3. 3.Department of AnatomyYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Macrogen Inc.SeoulRepublic of Korea
  5. 5.Department of Anatomy, Department of Otorhinolaryngology, BK21 PLUS Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea

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