JNK inhibition inhibits lateral line neuromast hair cell development

JNK signalling is known to play a role in regulating cell behaviours such as cell cycle progression, cell proliferation, and apoptosis, and recent studies have suggested important roles for JNK signalling in embryonic development. However, the precise function of JNK signalling in hair cell developm...

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Main Authors: Chengfu eCai, Jinchao elin, Shaoyang eSun, Yingzi eHe
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-02-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00019/full
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author Chengfu eCai
Chengfu eCai
Jinchao elin
Shaoyang eSun
Yingzi eHe
Yingzi eHe
author_facet Chengfu eCai
Chengfu eCai
Jinchao elin
Shaoyang eSun
Yingzi eHe
Yingzi eHe
author_sort Chengfu eCai
collection DOAJ
description JNK signalling is known to play a role in regulating cell behaviours such as cell cycle progression, cell proliferation, and apoptosis, and recent studies have suggested important roles for JNK signalling in embryonic development. However, the precise function of JNK signalling in hair cell development remains poorly studied. In this study, we used the small molecule JNK inhibitor SP600125 to examine the effect of JNK signalling abrogation on the development of hair cells in the zebrafish lateral line neuromast. Our results showed that SP600125 reduced the numbers of both hair cells and supporting cells in neuromasts during larval development in a dose-dependent manner. Additionally, JNK inhibition strongly inhibited the proliferation of neuromast cells, which likely explains the decrease in the number of differentiated hair cells in inhibitor-treated larvae. Furthermore, western blot and in situ analysis showed that JNK inhibition induced cell cycle arrest through induction of p21 expression. We also showed that SP600125 induced cell death in developing neuromasts as measured by cleaved caspase-3 immunohistochemistry, and this was accompanied with an induction of p53 gene expression. Together these results indicate that JNK might be an important regulator in the development of hair cells in the lateral line in zebrafish by controlling both cell cycle progression and apoptosis.
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spelling doaj.art-99ce8851866445fd975ab4a47f9cc8952022-12-22T01:22:51ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022016-02-011010.3389/fncel.2016.00019167976JNK inhibition inhibits lateral line neuromast hair cell developmentChengfu eCai0Chengfu eCai1Jinchao elin2Shaoyang eSun3Yingzi eHe4Yingzi eHe5Affiliated Eye and ENT Hospital of Fudan Universitythe First Affiliated Hospital, Xiamen UniversityQuanzhou First Hospital Affiliated to Fujian Medical UniversityKey Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical CollegeAffiliated Eye and ENT Hospital of Fudan UniversityAffiliated Eye and ENT Hospital of Fudan UniversityJNK signalling is known to play a role in regulating cell behaviours such as cell cycle progression, cell proliferation, and apoptosis, and recent studies have suggested important roles for JNK signalling in embryonic development. However, the precise function of JNK signalling in hair cell development remains poorly studied. In this study, we used the small molecule JNK inhibitor SP600125 to examine the effect of JNK signalling abrogation on the development of hair cells in the zebrafish lateral line neuromast. Our results showed that SP600125 reduced the numbers of both hair cells and supporting cells in neuromasts during larval development in a dose-dependent manner. Additionally, JNK inhibition strongly inhibited the proliferation of neuromast cells, which likely explains the decrease in the number of differentiated hair cells in inhibitor-treated larvae. Furthermore, western blot and in situ analysis showed that JNK inhibition induced cell cycle arrest through induction of p21 expression. We also showed that SP600125 induced cell death in developing neuromasts as measured by cleaved caspase-3 immunohistochemistry, and this was accompanied with an induction of p53 gene expression. Together these results indicate that JNK might be an important regulator in the development of hair cells in the lateral line in zebrafish by controlling both cell cycle progression and apoptosis.http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00019/fullZebrafishdevelopmentJNKHair cellSP600125
spellingShingle Chengfu eCai
Chengfu eCai
Jinchao elin
Shaoyang eSun
Yingzi eHe
Yingzi eHe
JNK inhibition inhibits lateral line neuromast hair cell development
Frontiers in Cellular Neuroscience
Zebrafish
development
JNK
Hair cell
SP600125
title JNK inhibition inhibits lateral line neuromast hair cell development
title_full JNK inhibition inhibits lateral line neuromast hair cell development
title_fullStr JNK inhibition inhibits lateral line neuromast hair cell development
title_full_unstemmed JNK inhibition inhibits lateral line neuromast hair cell development
title_short JNK inhibition inhibits lateral line neuromast hair cell development
title_sort jnk inhibition inhibits lateral line neuromast hair cell development
topic Zebrafish
development
JNK
Hair cell
SP600125
url http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00019/full
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AT jinchaoelin jnkinhibitioninhibitslaterallineneuromasthaircelldevelopment
AT shaoyangesun jnkinhibitioninhibitslaterallineneuromasthaircelldevelopment
AT yingziehe jnkinhibitioninhibitslaterallineneuromasthaircelldevelopment
AT yingziehe jnkinhibitioninhibitslaterallineneuromasthaircelldevelopment