Abstract
Histone deacetylase 1 (HDAC1) has been reported to be important for multiple aspects of normal embryonic development, but little is known about its function in the development of mechanosensory organs. Here, we first confirmed that HDAC1 is expressed in the developing otic vesicles of zebrafish by whole-mount in situ hybridization. Knockdown of HDAC1 using antisense morpholino oligonucleotides in zebrafish embryos induced smaller otic vesicles, abnormal otoliths, malformed or absent semicircular canals, and fewer sensory hair cells. HDAC1 loss of function also caused attenuated expression of a subset of key genes required for otic vesicle formation during development. Morpholino-mediated knockdown of HDAC1 resulted in decreased expression of members of the Fgf family in the otic vesicles, suggesting that HDAC1 is involved in the development of the inner ear through regulation of Fgf signaling pathways. Taken together, our results indicate that HDAC1 plays an important role in otic vesicle formation.
Highlights
Activation, while HDACs oppose the activity of HATs by removing acetyl groups from histone tails, which results in chromatin compaction and transcriptional repression[10]
At 48 hpf, we found that about 58% (98/169) of the Trichostatin A (TSA)-treated and 42% (43/103) of the valproic acid (VPA)-treated embryos exhibited a variety of abnormal otolith morphologies, including multiplication, aggregation, or ectopic location (Fig. 1a–c)
We observed that hair cell numbers in the maculae of HDAC inhibitors (HDACis)-treated embryos were reduced compared with control embryos at 48 hpf (Fig. 1d–f and Supplemental Figure 1a and e, p < 0 .05, analysis of variance (ANOVA))
Summary
Activation, while HDACs oppose the activity of HATs by removing acetyl groups from histone tails, which results in chromatin compaction and transcriptional repression[10]. The balance between the activities of HATs and HDACs is a critical regulator of cell differentiation, proliferation, and apoptosis and plays an important role in numerous developmental processes and disease states. HDAC1 activity is required to promote specification of neural progenitors in the developing brain by antagonizing the gene expression of Notch targets[17,22]. We report the association of HDAC1 activity with cell proliferation, cell survival, and the expression of hearing-associated genes. Taken together, these results indicate that the chromatin modification factor HDAC1 might be an important regulator of the formation and maintenance of auditory organs in zebrafish
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