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Unidirectional and stage-dependent roles of Notch1 in Wnt-responsive Lgr5+ cells during mouse inner ear development |
Hui Jiang1,3, Shan Zeng1,2, Wenli Ni1,2, Yan Chen1,2(), Wenyan Li1,2() |
1. ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, Fudan University, Shanghai 200031, China 2. Key Laboratory of Hearing Medicine of NHFPC, Shanghai 200031, China 3. Otorhinolaryngology Department of Jinshan Hospital, Fudan University, Shanghai 201508, China |
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Abstract Wnt and Notch signaling play crucial roles in the determination of the prosensory domain and in the differentiation of hair cells (HCs) and supporting cells during mouse inner ear development; however, the relationship between the two signaling pathways in the mouse cochlea remains largely unknown. Here, we investigated the interactions between Notch and Wnt signaling on the basis of the bidirectional regulation of Notch1 specifically in Wnt-responsive Lgr5+ progenitors during different cochlear development stages. We found that the downregulation of Notch1 in Lgr5+ cells from embryonic day (E) 14.5 to E18.5 can drive the quiescent Lgr5+ cells to re-enter the cell cycle and differentiate into extra HCs, whereas the upregulation of Notch1 expression did not affect the proliferation or differentiation of otic progenitor cells. No effect was observed on the upregulation or downregulation of Notch1 in Lgr5+ cells from E10.5 to E14.5. We concluded that the roles of Notch1 in Wnt-responsive Lgr5+ cells are unidirectional and stage dependent and Notch1 serves as a negative regulator for Lgr5+ progenitor activation during cochlear differentiation. Our findings improved the understanding of the interactions between Notch and Wnt signaling in cochlear development.
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Keywords
inner ear
cochlear
Wnt
Notch
Lgr5
auditory system
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Corresponding Author(s):
Yan Chen,Wenyan Li
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Just Accepted Date: 08 August 2019
Online First Date: 10 October 2019
Issue Date: 16 December 2019
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|
1 |
TT Whitfield. Development of the inner ear. Curr Opin Genet Dev 2015; 32: 112–118
https://doi.org/10.1016/j.gde.2015.02.006
pmid: 25796080
|
2 |
P Chen, JE Johnson, HY Zoghbi, N Segil. 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
|
3 |
YS Lee, F Liu, N Segil. A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development. Development 2006; 133(15): 2817–2826
https://doi.org/10.1242/dev.02453
pmid: 16790479
|
4 |
M Zak, SF Klis, W Grolman. 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(Pt B): 247–258
https://doi.org/10.1016/j.ijdevneu.2015.09.008
pmid: 26471908
|
5 |
R Chai, B Kuo, T Wang, EJ Liaw, A Xia, TA Jan, Z Liu, MM Taketo, JS Oghalai, R Nusse, J Zuo, AG Cheng. Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc Natl Acad Sci USA 2012; 109(21): 8167–8172
https://doi.org/10.1073/pnas.1202774109
pmid: 22562792
|
6 |
F Shi, L Hu, AS Edge. 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
https://doi.org/10.1073/pnas.1219952110
pmid: 23918377
|
7 |
BE Jacques, C Puligilla, RM Weichert, A Ferrer-Vaquer, AK Hadjantonakis, MW Kelley, A Dabdoub. A dual function for canonical Wnt/β-catenin signaling in the developing mammalian cochlea. Development 2012; 139(23): 4395–4404
https://doi.org/10.1242/dev.080358
pmid: 23132246
|
8 |
R Chai, A Xia, T Wang, TA Jan, T Hayashi, O Bermingham-McDonogh, AG Cheng. Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea. J Assoc Res Otolaryngol 2011; 12(4): 455–469
https://doi.org/10.1007/s10162-011-0267-2
pmid: 21472479
|
9 |
Y Zhang, Y Chen, W Ni, L Guo, X Lu, L Liu, W Li, S Sun, L Wang, H Li. Dynamic expression of Lgr6 in the developing and mature mouse cochlea. Front Cell Neurosci 2015; 9: 165
https://doi.org/10.3389/fncel.2015.00165
pmid: 26029045
|
10 |
BC Cox, R Chai, A Lenoir, Z Liu, L Zhang, DH Nguyen, K Chalasani, KA Steigelman, J Fang, EW Rubel, AG Cheng, J Zuo. Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development 2014; 141(4): 816–829
https://doi.org/10.1242/dev.103036
pmid: 24496619
|
11 |
R Chai, B Kuo, T Wang, EJ Liaw, A Xia, TA Jan, Z Liu, MM Taketo, JS Oghalai, R Nusse, J Zuo, AG Cheng. Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc Natl Acad Sci USA 2012; 109(21): 8167–8172
https://doi.org/10.1073/pnas.1202774109
pmid: 22562792
|
12 |
F Shi, JS Kempfle, AS Edge. Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea. J Neurosci 2012; 32(28): 9639–9648
https://doi.org/10.1523/JNEUROSCI.1064-12.2012
pmid: 22787049
|
13 |
T Wang, R Chai, GS Kim, N Pham, L Jansson, DH Nguyen, B Kuo, LA May, J Zuo, LL Cunningham, AG Cheng. Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle. Nat Commun 2015; 6(1): 6613
https://doi.org/10.1038/ncomms7613
pmid: 25849379
|
14 |
CS Jayasena, T Ohyama, N Segil, AK Groves. Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode. Development 2008; 135(13): 2251–2261
https://doi.org/10.1242/dev.017905
pmid: 18495817
|
15 |
A Zine, A Aubert, J Qiu, S Therianos, F Guillemot, R Kageyama, F de Ribaupierre. Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear. J Neurosci 2001; 21(13): 4712–4720
https://doi.org/10.1523/JNEUROSCI.21-13-04712.2001
pmid: 11425898
|
16 |
AK Lewis, GD Frantz, DA Carpenter, FJ de Sauvage, WQ Gao. Distinct expression patterns of notch family receptors and ligands during development of the mammalian inner ear. Mech Dev 1998; 78(1-2): 159–163
https://doi.org/10.1016/S0925-4773(98)00165-8
pmid: 9858718
|
17 |
AE Kiernan, J Xu, T Gridley. The Notch ligand JAG1 is required for sensory progenitor development in the mammalian inner ear. PLoS Genet 2006; 2(1): e4
https://doi.org/10.1371/journal.pgen.0020004
pmid: 16410827
|
18 |
N Yamamoto, K Tanigaki, M Tsuji, D Yabe, J Ito, T Honjo. Inhibition of Notch/RBP-J signaling induces hair cell formation in neonate mouse cochleas. J Mol Med (Berl) 2006; 84(1): 37–45
https://doi.org/10.1007/s00109-005-0706-9
pmid: 16283144
|
19 |
A Doetzlhofer, ML Basch, T Ohyama, M Gessler, AK Groves, N Segil. Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti. Dev Cell 2009; 16(1): 58–69
https://doi.org/10.1016/j.devcel.2008.11.008
pmid: 19154718
|
20 |
V Lin, JS Golub, TB Nguyen, CR Hume, EC Oesterle, JS Stone. Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles. J Neurosci 2011; 31(43): 15329–15339
https://doi.org/10.1523/JNEUROSCI.2057-11.2011
pmid: 22031879
|
21 |
K Mizutari, M Fujioka, M Hosoya, N Bramhall, HJ Okano, H Okano, ASB Edge. Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron 2013; 77(1): 58–69
https://doi.org/10.1016/j.neuron.2012.10.032
pmid: 23312516
|
22 |
JL Zheng, J Shou, F Guillemot, R Kageyama, WQ Gao. Hes1 is a negative regulator of inner ear hair cell differentiation. Development 2000; 127(21): 4551–4560
pmid: 11023859
|
23 |
N Daudet, R Gibson, J Shang, A Bernard, J Lewis, J Stone. Notch regulation of progenitor cell behavior in quiescent and regenerating auditory epithelium of mature birds. Dev Biol 2009; 326(1): 86–100
https://doi.org/10.1016/j.ydbio.2008.10.033
pmid: 19013445
|
24 |
W Li, J Wu, J Yang, S Sun, R Chai, ZY Chen, H Li. Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway. Proc Natl Acad Sci USA 2015; 112(1): 166–171
https://doi.org/10.1073/pnas.1415901112
pmid: 25535395
|
25 |
W Ni, C Lin, L Guo, J Wu, Y Chen, R Chai, W Li, H Li. Extensive supporting cell proliferation and mitotic hair cell generation by in vivo genetic reprogramming in the neonatal mouse cochlea. J Neurosci 2016; 36(33): 8734–8745
https://doi.org/10.1523/JNEUROSCI.0060-16.2016
pmid: 27535918
|
26 |
BH Hartman, TA Reh, O Bermingham-McDonogh. Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear. Proc Natl Acad Sci USA 2010; 107(36): 15792–15797
https://doi.org/10.1073/pnas.1002827107
pmid: 20798046
|
27 |
W Pan, Y Jin, B Stanger, AE Kiernan. 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
https://doi.org/10.1073/pnas.1003089107
pmid: 20733081
|
28 |
W Pan, Y Jin, J Chen, RJ Rottier, KP Steel, AE Kiernan. Ectopic expression of activated notch or SOX2 reveals similar and unique roles in the development of the sensory cell progenitors in the mammalian inner ear. J Neurosci 2013; 33(41): 16146–16157
https://doi.org/10.1523/JNEUROSCI.3150-12.2013
pmid: 24107947
|
29 |
Z Liu, T Owen, J Fang, J Zuo. Overactivation of Notch1 signaling induces ectopic hair cells in the mouse inner ear in an age-dependent manner. PLoS One 2012; 7(3): e34123
https://doi.org/10.1371/journal.pone.0034123
pmid: 22448289
|
30 |
C Cheng, L Guo, L Lu, XC Xu, SS Zhang, JY Gao, M Waqas, CW Zhu, Y Chen, XL Zhang, CY Xuan, X Gao, ML Tang, FY Chen, HB Shi, HW Li, RJ Chai. Characterization of the transcriptomes of Lgr5+ hair cell progenitors and Lgr5− supporting cells in the mouse cochlea. Front Mol Neurosci 2017; 10: 122
https://doi.org/10.3389/fnmol.2017.00122
|
31 |
J Petrovic, P Formosa-Jordan, JC Luna-Escalante, G Abelló, M Ibañes, J Neves, F Giraldez. Ligand-dependent Notch signaling strength orchestrates lateral induction and lateral inhibition in the developing inner ear. Development 2014; 141(11): 2313–2324
https://doi.org/10.1242/dev.108100
pmid: 24821984
|
32 |
Z Liu, Z Liu, BJ Walters, T Owen, R Kopan, J Zuo. In vivo visualization of Notch1 proteolysis reveals the heterogeneity of Notch1 signaling activity in the mouse cochlea. PLoS One 2013; 8(5): e64903
https://doi.org/10.1371/journal.pone.0064903
pmid: 23741415
|
33 |
PJ Atkinson, Y Dong, S Gu, W Liu, EH Najarro, T Udagawa, AG Cheng. Sox2 haploinsufficiency primes regeneration and Wnt responsiveness in the mouse cochlea. J Clin Invest 2018; 128(4): 1641–1656
https://doi.org/10.1172/JCI97248
pmid: 29553487
|
34 |
J Waldhaus, R Durruthy-Durruthy, S Heller. Quantitative high-resolution cellular map of the organ of Corti. Cell Reports 2015; 11(9): 1385–1399
https://doi.org/10.1016/j.celrep.2015.04.062
pmid: 26027927
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