The Glutamine Synthetases Are Required for Sensory Hair Cell Formation and Auditory Function in Zebrafish

The development of sensory hair cells (HCs) is closely linked to hearing loss. There are still many unidentified genes that may play a crucial role in HC development and function. Glutamine synthetase, Glul, is expressed in sensory hair cells and auditory organs. However, the role of the <i>Glul</i> gene family in the auditory system remains largely unexplored. This study aims to investigate the function of the <i>Glul</i> gene family in the auditory system. The expression patterns of the <i>glul</i> gene family were examined via in situ hybridization in zebrafish embryos. It was revealed that the expression of <i>glula</i> occurred in the otic vesicle, while <i>glulb</i> was expressed in the neuromast. In contrast, <i>glulc</i> did not exhibit any discernible signal. <i>glula</i> loss of function caused abnormal otolith formation and reduced hair cell number in otic vesicles, while <i>glulb</i> knockdown caused a decrease in HC number in both neuromasts and otic vesicles and impaired auditory function. Furthermore, we found that the knockdown of <i>glulb</i> induces apoptosis of hair cells. Transcriptomic analysis of zebrafish with <i>glula</i> and <i>glulb</i> knockdown revealed significant alterations in the expression of many genes associated with auditory organs. The current study sheds light on the requirement of <i>glula</i> and <i>glulb</i> in zebrafish hair cell formation and auditory function.