Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2016, Vol. 10 Issue (3) : 330-335    https://doi.org/10.1007/s11684-016-0459-6
RESEARCH ARTICLE
Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium
Yan Chen1,2,3,Wenyan Li1,3,Wen Li1,2,3,Renjie Chai4,5,*(),Huawei Li1,3,6,*()
1. Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, China
2. Central Laboratory, Affiliated Eye and ENT Hospital, Fudan University, Shanghai 200031, China
3. Key Laboratory of Hearing Medicine of the National Health and Family Planning Commission, Shanghai 200031, China
4. MOE Key Laboratory of Developmental Genes and Human Disease, State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing 210096, China
5. Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
6. Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
 Download: PDF(311 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

The enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) is a histone-lysine N-methyltransferase enzyme that participates in DNA methylation. Ezh2 has also been reported to play crucial roles in stem cell proliferation and differentiation. However, the detailed expression profile of Ezh2 during mouse cochlear development has not been investigated. Here, we examined the spatiotemporal expression of Ezh2 in the cochlea during embryonic and postnatal development. Ezh2 expression began to be observed in the whole otocyst nuclei at embryonic day 9.5 (E9.5). At E12.5, Ezh2 was expressed in the nuclei of the cochlear prosensory epithelium. At E13.5 and E15.5, Ezh2 was expressed from the apical to the basal turns in the nuclei of the differentiating cochlear epithelium. At postnatal day (P) 0 and 7, the Ezh2 expression was located in the nuclei of the cochlear epithelium in all three turns and could be clearly seen in outer and inner hair cells, supporting cells, the stria vascularis, and spiral ganglion cells. Ezh2 continued to be expressed in the cochlear epithelium of adult mice. Our results provide the basic Ezh2 expression pattern and might be useful for further investigating the detailed role of Ezh2 during cochlear development.

Keywords polycomb repressive complex      Ezh2      expression      inner ear      cochlea      development     
Corresponding Author(s): Renjie Chai,Huawei Li   
Just Accepted Date: 07 July 2016   Online First Date: 27 July 2016    Issue Date: 30 August 2016
 Cite this article:   
Yan Chen,Wenyan Li,Wen Li, et al. Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium[J]. Front. Med., 2016, 10(3): 330-335.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-016-0459-6
https://academic.hep.com.cn/fmd/EN/Y2016/V10/I3/330
Fig.1  Ezh2 was expressed in the otocyst at E9.5 and E10.5. Triple immunofluorescence staining showed that Ezh2 staining was located in the nuclei of the whole otocyst.
Fig.2  Ezh2 was expressed in the developing cochlear duct. Representative images of E12.5 (A), E13.5 (B), and E15.5 (C) cochlear epithelium are shown.
Fig.3  Ezh2 was expressed in the sensory epithelium and the spiral ganglion at P0. (A) The image shows obvious Ezh2 staining in the cochlear sensory epithelium, the stria vascularis, and the spiral ganglion at low magnification. The arrows indicate the spiral ganglions. (B) The images show that Ezh2 was expressed in the Kölliker organ, inner and outer hair cells, and supporting cells. OHCs, outer hair cells; IHC, inner hair cell.
Fig.4  Ezh2 was expressed in the cochlear sensory epithelium at P7. Myosin 7a and Ezh2 staining (A) showed that Ezh2 was expressed in the inner and outer hair cells. Sox2 and Ezh2 staining (B) showed that Ezh2 was expressed in all supporting cells.
Fig.5  Ezh2 was expressed in the cochlear sensory epithelium at P35. Parvalbumin and Ezh2 staining (A) showed that Ezh2 was expressed in the inner and outer hair cells. Sox2 and Ezh2 staining (B) showed that Ezh2 was expressed in all supporting cells. OHCs, outer hair cells; IHC, inner hair cell. Negative control images with primary antibody omission are also shown (C).
1 Layman WS, Zuo J. Epigenetic regulation in the inner ear and its potential roles in development, protection, and regeneration. Front Cell Neurosci 2014; 8: 446
pmid: 25750614
2 Uribe RA, Buzzi AL, Bronner ME, Strobl-Mazzulla PH. Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression. J Cell Biol 2015; 211(4): 815–827
https://doi.org/10.1083/jcb.201503071 pmid: 26598618
3 Hurd EA, Poucher HK, Cheng K, Raphael Y, Martin DM. The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear. Development 2010; 137(18): 3139–3150
https://doi.org/10.1242/dev.047894 pmid: 20736290
4 Roellig D, Bronner ME. The epigenetic modifier DNMT3A is necessary for proper otic placode formation. Dev Biol 2016; 411(2): 294–300
https://doi.org/10.1016/j.ydbio.2016.01.034 pmid: 26826496
5 Stojanova ZP, Kwan T, Segil N. Epigenetic regulation of Atoh1 guides hair cell development in the mammalian cochlea. Development 2015; 142(20): 3529–3536
https://doi.org/10.1242/dev.126763 pmid: 26487780
6 Viré E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006; 439(7078): 871–874
https://doi.org/10.1038/nature04431 pmid: 16357870
7 Morey L, Helin K. Polycomb group protein-mediated repression of transcription. Trends Biochem Sci 2010; 35(6): 323–332
https://doi.org/10.1016/j.tibs.2010.02.009 pmid: 20346678
8 Ezhkova E, Pasolli HA, Parker JS, Stokes N, Su IH, Hannon G, Tarakhovsky A, Fuchs E. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell 2009; 136(6): 1122–1135
https://doi.org/10.1016/j.cell.2008.12.043 pmid: 19303854
9 Juan AH, Derfoul A, Feng X, Ryall JG, Dell’Orso S, Pasut A, Zare H, Simone JM, Rudnicki MA, Sartorelli V. Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells. Genes Dev 2011; 25(8): 789–794
https://doi.org/10.1101/gad.2027911 pmid: 21498568
10 Yin J, Leavenworth JW, Li Y, Luo Q, Xie H, Liu X, Huang S, Yan H, Fu Z, Zhang LY, Zhang L, Hao J, Wu X, Deng X, Roberts CW, Orkin SH, Cantor H, Wang X. Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity. Proc Natl Acad Sci USA 2015; 112(52): 15988–15993
https://doi.org/10.1073/pnas.1521740112 pmid: 26668377
11 Jing H, Liao L, An Y, Su X, Liu S, Shuai Y, Zhang X, Jin Y. Suppression of EZH2 prevents the shift of osteoporotic MSC fate to adipocyte and enhances bone formation during osteoporosis. Mol Ther 2016; 24(2): 217–229
https://doi.org/10.1038/mt.2015.152 pmid: 26307668
12 Yoo KH, Oh S, Kang K, Hensel T, Robinson GW, Hennighausen L. Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes. Nucleic Acids Res 2015; 43(18): 8774–8789
https://doi.org/10.1093/nar/gkv776 pmid: 26250110
13 Mochizuki-Kashio M, Aoyama K, Sashida G, Oshima M, Tomioka T, Muto T, Wang C, Iwama A. Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-dependent manner. Blood 2015; 126(10): 1172–1183
https://doi.org/10.1182/blood-2015-03-634428 pmid: 26219303
14 Snitow ME, Li S, Morley MP, Rathi K, Lu MM, Kadzik RS, Stewart KM, Morrisey EE. Ezh2 represses the basal cell lineage during lung endoderm development. Development 2015; 142(1): 108–117
https://doi.org/10.1242/dev.116947 pmid: 25516972
15 Galvis LA, Holik AZ, Short KM, Pasquet J, Lun AT, Blewitt ME, Smyth IM, Ritchie ME, Asselin-Labat ML. Repression of Igf1 expression by Ezh2 prevents basal cell differentiation in the developing lung. Development 2015; 142(8): 1458–1469
https://doi.org/10.1242/dev.122077 pmid: 25790853
16 Zhang J, Ji F, Liu Y, Lei X, Li H, Ji G, Yuan Z, Jiao J. Ezh2 regulates adult hippocampal neurogenesis and memory. J Neurosci 2014; 34(15): 5184–5199
https://doi.org/10.1523/JNEUROSCI.4129-13.2014 pmid: 24719098
17 Juan AH, Kumar RM, Marx JG, Young RA, Sartorelli V. Mir-214-dependent regulation of the polycomb protein Ezh2 in skeletal muscle and embryonic stem cells. Mol Cell 2009; 36(1): 61–74
https://doi.org/10.1016/j.molcel.2009.08.008 pmid: 19818710
18 Chen Y, Li L, Ni W, Zhang Y, Sun S, Miao D, Chai R, Li H.Bmi1 regulates auditory hair cell survival by maintaining redox balance. Cell Death Dis 2015; 6: e1605
https://doi.org/10.1038/cddis.2014.549 pmid: 25611380
19 Lu X, Sun S, Qi J, Li W, Liu L, Zhang Y, Chen Y, Zhang S, Wang L, Miao D, Chai R, Li H. Bmi1 regulates the proliferation of cochlear supporting cells via the canonical Wnt signaling pathway. Mol Neurobiol <Date>2016 Feb 3</Date>. [Epub ahead of print] PMID: 26843109 DOI: 10.1007/s12035-016-9686-8
https://doi.org/10.1007/s12035-016-9686-8
20 Radde-Gallwitz K, Pan L, Gan L, Lin X, Segil N, Chen P. Expression of Islet1 marks the sensory and neuronal lineages in the mammalian inner ear. J Comp Neurol 2004; 477(4): 412–421
https://doi.org/10.1002/cne.20257 pmid: 15329890
21 Morsli H, Choo D, Ryan A, Johnson R, Wu DK. Development of the mouse inner ear and origin of its sensory organs. J Neurosci 1998; 18(9): 3327–3335
pmid: 9547240
22 Chen P, Johnson JE, Zoghbi HY, Segil N. The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination. Development 2002; 129(10): 2495–2505
pmid: 11973280
23 Fekete DM, Muthukumar S, Karagogeos D. Hair cells and supporting cells share a common progenitor in the avian inner ear. J Neurosci 1998; 18(19): 7811–7821
pmid: 9742150
24 Simon JA, Kingston RE. Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol 2009; 10(10): 697–708
pmid: 19738629
25 Kim KH, Roberts CW. Targeting EZH2 in cancer. Nat Med 2016; 22(2): 128–134
https://doi.org/10.1038/nm.4036 pmid: 26845405
26 Yoo KH, Hennighausen L. EZH2 methyltransferase and H3K27 methylation in breast cancer. Int J Biol Sci 2012; 8(1): 59–65
https://doi.org/10.7150/ijbs.8.59 pmid: 22211105
27 Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA, Chinnaiyan AM. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002; 419(6907): 624–629
https://doi.org/10.1038/nature01075 pmid: 12374981
28 Zingg D, Debbache J, Schaefer SM, Tuncer E, Frommel SC, Cheng P, Arenas-Ramirez N, Haeusel J, Zhang Y, Bonalli M, McCabe MT, Creasy CL, Levesque MP, Boyman O, Santoro R, Shakhova O, Dummer R, Sommer L. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun 2015; 6: 6051
https://doi.org/10.1038/ncomms7051 pmid: 25609585
29 Arisan S, Buyuktuncer ED, Palavan-Unsal N, Caşkurlu T, Cakir OO, Ergenekon E. Increased expression of EZH2, a polycomb group protein, in bladder carcinoma. Urol Int 2005; 75(3): 252–257
https://doi.org/10.1159/000087804 pmid: 16215315
30 Lund K, Adams PD, Copland M. EZH2 in normal and malignant hematopoiesis. Leukemia 2014; 28(1): 44–49
https://doi.org/10.1038/leu.2013.288 pmid: 24097338
31 Layman WS, Sauceda MA, Zuo J. Epigenetic alterations by NuRD and PRC2 in the neonatal mouse cochlea. Hear Res 2013; 304: 167–178
https://doi.org/10.1016/j.heares.2013.07.017 pmid: 23911933
[1] Jing Ma, Shiyu Chen, Lili Hao, Wei Sheng, Weicheng Chen, Xiaojing Ma, Bowen Zhang, Duan Ma, Guoying Huang. Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation by targeting HAND2[J]. Front. Med., 2021, 15(1): 91-100.
[2] Dongping Ning, Zhan Zhang, Kun Qiu, Lin Lu, Qin Zhang, Yan Zhu, Renzhi Wang. Efficacy of intelligent diagnosis with a dynamic uncertain causality graph model for rare disorders of sex development[J]. Front. Med., 2020, 14(4): 498-505.
[3] Hui Jiang, Shan Zeng, Wenli Ni, Yan Chen, Wenyan Li. Unidirectional and stage-dependent roles of Notch1 in Wnt-responsive Lgr5+ cells during mouse inner ear development[J]. Front. Med., 2019, 13(6): 705-712.
[4] Han Wang, Hong Zhou, Yan Zhang, Yan Wang, Jing Sun. Association of maternal depression with dietary intake, growth, and development of preterm infants: a cohort study in Beijing, China[J]. Front. Med., 2018, 12(5): 533-541.
[5] Zhaoyun Zhu, Yali Gui, Li Wang, Ting Wang, Yang Yang, Yunzhuang Niu, Dehuan Fu, Jingkun Wang, Tao Cui. Innovative development path of ethnomedicines: a case study[J]. Front. Med., 2017, 11(2): 297-305.
[6] Zhaoyun Zhu,Dehuan Fu,Yali Gui,Tao Cui,Jingkun Wang,Ting Wang,Zhizhong Yang,Yanfei Niu,Zhennan She,Li Wang. Innovative development path of ethnomedicines: the interpretation of the path[J]. Front. Med., 2017, 11(1): 32-47.
[7] Liangyun Zhou,Guang Yang,Haifeng Sun,Jinfu Tang,Jian Yang,Yizhan Wang,Thomas Avery Garran,Lanping Guo. Effects of different doses of cadmium on secondary metabolites and gene expression in Artemisia annua L.[J]. Front. Med., 2017, 11(1): 137-146.
[8] Yunfang Liu,Zhiping Yang,Jing Cheng,Daiming Fan. Barriers and countermeasures in developing traditional Chinese medicine in Europe[J]. Front. Med., 2016, 10(3): 360-376.
[9] Yujiao Liu,Chao Liu,Wen Dong,Wei Li. Physiological functions and clinical implications of the N-end rule pathway[J]. Front. Med., 2016, 10(3): 258-270.
[10] Yanfei Wang,Yueyue Liu,Hongyun Nie,Xin Ma,Zhigang Xu. Alternative splicing of inner-ear-expressed genes[J]. Front. Med., 2016, 10(3): 250-257.
[11] Muhammad Waqas,Shasha Zhang,Zuhong He,Mingliang Tang,Renjie Chai. Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea[J]. Front. Med., 2016, 10(3): 237-249.
[12] Xinsen Xu,Yanyan Zhou,Runchen Miao,Wei Chen,Kai Qu,Qing Pang,Chang Liu. Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis[J]. Front. Med., 2016, 10(2): 183-190.
[13] Zhaoyun Zhu,Ting Wang,Dehuan Fu,Yali Gui,Jingkun Wang,Tao Cui. Innovative development path of ethnomedicines: an overview of ethnomedicines in China[J]. Front. Med., 2016, 10(2): 166-177.
[14] Yanfang Pan,Lijun Xia. Emerging roles of podoplanin in vascular development and homeostasis[J]. Front. Med., 2015, 9(4): 421-430.
[15] Raafat Hegazy,Abdelmonem Hegazy,Mustafa Ammar,Emad Salem. Immunohistochemical measurement and expression of Mcl-1 in infertile testes[J]. Front. Med., 2015, 9(3): 361-367.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed