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Loss of ndrg2 Function Is Involved in Notch Activation in Neuromast Hair Cell Regeneration in Zebrafish

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Abstract

The regeneration of hair cells in zebrafish is a complex process involving the precise regulation of multiple signaling pathways, but this complicated regulatory network is not fully understood. Current research has primarily focused on finding molecules and pathways that can regulate hair cell regeneration and restore hair cell functions. Here, we show the role of N-Myc downstream regulated gene 2 (ndrg2) in zebrafish hair cell regeneration. We first found that ndrg2 was dynamically expressed in neuromasts of the developing zebrafish, and this expression was increased after neomycin-induced hair cell damage. Then, ndrg2 loss-of-function larvae showed reduced numbers of regenerated hair cells but increased numbers of supporting cells after neomycin exposure. By in situ hybridization, we further observed that ndrg2 loss of function resulted in the activation of Notch signaling and downregulation of atoh1a during hair cell regeneration in vivo. Additionally, blocking Notch signaling rescued the number of regenerated hair cells in ndrg2-deficient larvae. Together, this study provides evidence for the role of ndrg2 in regulating hair cell regeneration in zebrafish neuromasts.

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The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 82192860, 82192862, 81830029, 81970879), the Natural Science Foundation of China (2018YFA0801004), the Shanghai Science and Technology Committee (STCSM) Science and Technology Innovation Program (No. 20MC1920200), and the Research Projects of the Shanghai Municipal Health Committee (2020YJZX0110, 2022XD059).

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  1. Xin Wang, Xiaodong Gu, and Cheng Wang contributed equally to this work.

Authors and Affiliations

  1. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China

    Xin Wang & Huawei Li

  2. Department of ENT Institute and Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai, 200031, People’s Republic of China

    Xin Wang, Xiaodong Gu, Yingzi He, Shan Sun & Huawei Li

  3. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China

    Xin Wang

  4. Nantong Laboratory of Development and Diseases, School of Life Sciences, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China

    Xin Wang, Cheng Wang & Dong Liu

  5. The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, People’s Republic of China

    Huawei Li

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  1. Xin Wang
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All authors made a significant contribution to the work reported, whether in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.

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Correspondence to Dong Liu, Shan Sun or Huawei Li.

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Wang, X., Gu, X., Wang, C. et al. Loss of ndrg2 Function Is Involved in Notch Activation in Neuromast Hair Cell Regeneration in Zebrafish. Mol Neurobiol 60, 3100–3112 (2023). https://doi.org/10.1007/s12035-023-03262-6

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