Abstract
Histone demethylase PHF8 is crucial for multiple developmental processes, and hence, the awareness of its function in developing auditory organs needs to be increased. Using in situ hybridization (ISH) labeling, the mRNA expression of PHF8 in the zebrafish lateral line system and otic vesicle was monitored. The knockdown of PHF8 by morpholino significantly disrupted the development of the posterior lateral line system, which impacted cell migration and decreased the number of lateral line neuromasts. The knockdown of PHF8 also resulted in severe malformation of the semicircular canal and otoliths in terms of size, quantity, and position during the inner ear development. The loss of function of PHF8 also induced a defective differentiation in sensory hair cells in both lateral line neuromasts and the inner ear. ISH analysis of embryos that lacked PHF8 showed alterations in the expression of many target genes of several signaling pathways concerning cell migration and deposition, including the Wnt and FGF pathways. In summary, the current findings established PHF8 as a novel epigenetic element in developing auditory organs, rendering it a potential candidate for hearing loss therapy.
Highlights
A primary cause of hearing loss is the abnormal development of inner ear structure, which is a highly dynamic process that includes modeling, cellular growth, migration, and differentiation
The present study reported that PHF8 is significant for developing the posterior lateral line (pLL) and inner ear in zebrafish
We found that PHF8 is highly expressed in the primordium of pLL and in the otic vesicle, which implicates that it may play a role in the hearing procedure
Summary
A primary cause of hearing loss is the abnormal development of inner ear structure, which is a highly dynamic process that includes modeling, cellular growth, migration, and differentiation. Several regulators concerning the inner ear’s development have been the subject of studies, knowledge of the underlying molecular mechanisms is still incomplete. Epigenetic mechanisms, such as histone modifications, are essential in the development process of the auditory system (He et al, 2013, 2014, 2016a,b, 2020). It is believed that the histone deacetylases (HDACs) act as transcriptional regulators, modulating the differentiation and proliferation of hair cells during auditory organogenesis in zebrafish (He et al, 2016b). A complete understanding of the epigenetic changes in the development, physiology, and pathology of hearing would be of great importance, with potential applications in preventing and treating hearing loss in humans
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