Trans-2-phenylcyclopropylamine regulates zebrafish lateral line neuromast development mediated by depression of LSD1 activity.

The zebrafish mechanosensory lateral line (LL) is a model system for the study of hair cell development, survival and regeneration. Recently, histone modifications have attracted a considerable amount of interest because of their indispensable roles in various kinds of cellular processes including differentiation, proliferation, apoptosis and function. Lysine specific demethylase 1 (LSD1) is an important enzyme that regulates histone methylation. As a transcriptional regulator, this enzyme has broad functional activities and is involved in many biological processes. However, the effects of LSD1 on the early development of zebrafish sensory system have not been fully elucidated. Here, we have found that pharmacological inhibition of LSD1 with the monoamine oxidase (MAO) inhibitor trans-2-phenylcyclopropylamine (referred to as 2-PCPA) reduced the numbers of both sensory hair cells and supporting cells of neuromasts during zebrafish development. Our results showed that the treatment of zebrafish larvae with 2-PCPA caused accumulation of histone methylation and suppressed proliferation of neuromast cells. Finally, acridine orange staining assay demonstrated that 2-PCPA treatment at high concentrations induced an enhancement of cellular apoptosis within neuromasts. Taken together, these results indicate that LSD1 demethylase activity is required for neuromast development in zebrafish larvae.