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The ndrg2 Gene Regulates Hair Cell Morphogenesis and Auditory Function during Zebrafish Development
Cheng Wang1, Xin Wang2, Hao Zheng3
1Nantong Laboratory of Development and Diseases, School of Life Sciences, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
International Journal of Molecular Sciences
|June 28, 2023
Summary
N-myc downstream-regulated gene 2 (ndrg2) is crucial for hair cell development and hearing function in zebrafish. Loss of ndrg2 impairs hair cell numbers and auditory responses, highlighting its role in preventing hearing loss.
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.
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