title: Role of histone deacetylase activity in the developing lateral line neuromast of zebrafish larvae.
abstract: Histone deacetylases are involved in many biological processes and have roles in regulating cell behaviors such as cell cycle entry, cell proliferation and apoptosis. However, the effect of histone deacetylases on the development of hair cells (HCs) has not been fully elucidated. In this study, we examined the influence of histone deacetylases on the early development of neuromasts in the lateral line of zebrafish. Hair cell development was evaluated by fluorescent immunostaining in the absence or presence of histone deacetylase inhibitors. Our results suggested that pharmacological inhibition of histone deacetylases with inhibitors, including trichostatin A, valproic acid and MS-275, reduced the numbers of both HCs and supporting cells in neuromasts. We also found that the treatment of zebrafish larvae with inhibitors caused accumulation of histone acetylation and suppressed proliferation of neuromast cells. Real-time PCR results showed that the expression of both p21 and p27 mRNA was increased following trichostatin A treatment and the increase in p53 mRNA was modest under the same conditions. However, the expression of p53 mRNA was significantly increased by treatment with a high concentration of trichostatin A. A high concentration of trichostatin A also led to increased cell death in neuromasts as detected in a TUNEL assay. Moreover, the nuclei of most of these pyknotic cells were immunohistochemically positive for cleaved caspase-3. These results suggest that histone deacetylase activity is involved in lateral line development in the zebrafish and might have a role in neuromast formation by altering cell proliferation through the expression of cell cycle regulatory proteins.
authors.affiliation: 1] Department of Otology Skull Base Surgery, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai, China [2] Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Otology Skull Base Surgery, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Otology Skull Base Surgery, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai, China.
authors.forename: Huiqian
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Otology Skull Base Surgery, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Otology Skull Base Surgery, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Ni
authors.affiliation: 1] Department of Otology Skull Base Surgery, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai, China [2] Institutes of Biomedical Sciences, Fudan University, Shanghai, China [3] State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D053403:Lateral Line System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D006655:Histone Deacetylases