The ndrg2 Gene Regulates Hair Cell Morphogenesis and Auditory Function during Zebrafish Development

Area of Science:

• Developmental Biology
• Genetics
• Neuroscience

Background:

• Sensorineural hearing loss stems from sensory hair cell damage, with many causative genes yet to be identified.
• N-myc downstream-regulated gene 2 (ndrg2) is known for its roles in cell stress and tumor suppression, but its function in auditory hair cell development is unclear.

Purpose of the Study:

• To investigate the role of ndrg2 in zebrafish hair cell (HC) development and auditory function.
• To elucidate the molecular mechanisms underlying ndrg2's function in HC morphogenesis.

Main Methods:

• In situ hybridization and single-cell RNA sequencing to determine ndrg2 expression patterns in HCs.
• Generating ndrg2 loss-of-function zebrafish larvae to observe effects on HC development and auditory behavior.
• Rescue experiments using ndrg2 mRNA microinjection and Notch signaling pathway inhibition.

Main Results:

• Ndrg2 is highly expressed in zebrafish otic vesicle and neuromast HCs.
• Ndrg2 deficiency leads to reduced HCs, shortened cilia, fewer neuromasts, and impaired auditory startle responses.
• The observed defects were rescued by ndrg2 mRNA injection, and Notch signaling pathway inhibition partially restored HC function, indicating ndrg2's role in Notch-mediated HC differentiation.

Conclusions:

• Ndrg2 is essential for normal hair cell development and auditory sensory function in zebrafish.
• This study identifies ndrg2 as a potential deafness gene and sheds light on the regulation of HC development via the Notch pathway.