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.

NeuO: a Fluorescent Chemical Probe for Live Neuron Labeling

“…[15] Neuromasts make up part of the lateral lines system in zebrafish, which are comprised of a set of rosette- like organs near the head and the body ( Figure S9c). [16] These data demonstrate that NeuOs neuronal staining is conserved across species.…”

Using Zebrafish to Study Human Deafness and Hearing Regeneration

“…Since pho is a novel gene with no obvious homologs, its molecular function remains unclear. The stat3 pathway [77] and histone deacetylases (HDAC) [94] have been reported playing a role in hair cell regeneration. However, results were obtained from morpholino or pharmaceutical approaches, and given recent evidence that morpholino-generated phenotypes are often misleading [59], these results will need to be further validated with genetic mutations.…”

Valeriana Officinalis Crude Extracts Impair Hair Cell Regeneration in Larval Zebrafish Lateral Line

“…VA led to the synthesis of a powerful chemical analog named valproate (or valproic acid, VPA) which is the top-prescribed psychoactive drug worldwide (28). More relevant here, VPA was also shown to severely reduce LL-HC regeneration in zebrafish larvae (29,30). Our rationale was that if Val is not toxic, it would contain enough VA to elicit comparable effects to purified synthetic VPA, and therefore demonstrate that a non-purified active compound when present in a complex mixture can be detected with the proposed screening assay.…”

“…Our rationale was that if Val is not toxic, it would contain enough VA to elicit comparable effects to purified synthetic VPA, and therefore demonstrate that a non-purified active compound when present in a complex mixture can be detected with the proposed screening assay. Consequently, after ablating all HCs in 5dpf larvae, we treated them with 150M VPA (VPA150) as previously published (29,30), or with the highest well-tolerated concentration of Val (Val1=1mg/ml) for the following 3 days. We found a significant decrease in HC-regeneration with both treatments which was not due to HC toxicity of neither treatment, suggesting a similar mode of action.…”