title: JNK Inhibition Inhibits Lateral Line Neuromast Hair Cell Development.
abstract: JNK signaling is known to play a role in regulating cell behaviors such as cell cycle progression, cell proliferation, and apoptosis, and recent studies have suggested important roles for JNK signaling in embryonic development. However, the precise function of JNK signaling in hair cell development remains poorly studied. In this study, we used the small molecule JNK inhibitor SP600125 to examine the effect of JNK signaling 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.
authors.affiliation: Department of Otolaryngology, Affiliated Eye and ENT Hospital of Fudan UniversityShanghai, China; Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Xiamen UniversityXiamen, Fujian, China.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University Quanzhou, Fujian, China.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Medical Sciences, School of Basic Medical Sciences, Fudan University Shanghai, China.
authors.forename: Shaoyang
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, Affiliated Eye and ENT Hospital of Fudan UniversityShanghai, China; Research Center, Affiliated Eye and ENT Hospital of Fudan UniversityShanghai, China; Key Laboratory of Hearing Medicine, Ministry of Health, Affiliated Eye and ENT Hospital of Fudan UniversityShanghai, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: He
keywords: JNK; SP600125; development; hair cell; zebrafish