Chemical screening reveals Ronidazole is a superior prodrug to Metronidazole for nitroreductase-induced cell ablation system in zebrafish larvae

Siting Lai; Ankita Kumari; Jixiang Liu; Yiyue Zhang; Wenqing Zhang; Kuangyu Yen; Jin Xu

doi:10.1016/j.jgg.2021.07.015

Volume 48 Issue 12

Dec. 2021

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Article Navigation > Journal of Genetics and Genomics > 2021 > 48(12): 1081-1090

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Chemical screening reveals Ronidazole is a superior prodrug to Metronidazole for nitroreductase-induced cell ablation system in zebrafish larvae

doi: 10.1016/j.jgg.2021.07.015

a. Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China;
b. Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China

Funds:

We thank Dr. Hae-Chul Park for providing Tg(UAS:Eco.NfsBmCherry) transgenic line

Dr. Zilong Wen for providing Tg(mpeg1.1:GFP-NTR) transgenic line and the krtt1c19e construct. Dr. Fei Jifeng for providing mCherry-T2AwtNTR and mCherry-T2A-mutNTR construct. This work was supported by the National Natural Science Foundation of China (31771594, 31970763), National Natural Science Foundation of China (NSFC)/Research Grants Council (RGC) Joint Research Scheme (31961160726), and Guangdong Science and Technology Plan projects (2019A030317001).

Dr. Koichi Kawakami for providing Tg(hsp:Gal4FF62A) transgenic line and Gal4FF construct

Dr. David Raible for providing TgBAC(neurod1:EGFP) transgenic line

Received Date: 2021-01-16
Accepted Date: 2021-07-26
Rev Recd Date: 2021-07-21
Publish Date: 2021-12-20

Abstract

Abstract

The Metronidazole (MTZ)/nitroreductase (NTR)-mediated cell ablation system is the most commonly used chemical-genetic cell ablation method in zebrafish. This system can specifically ablate target cells under spatial and temporal control. The MTZ/NTR system has become a widely used cell ablation system in biological, developmental, and functional studies. However, the inadequate cell-ablation ability of some cell types and the side effects of high concentration MTZ impede extensive applications of the MTZ/NTR system. In the present study, the US drug collection library was searched to extend the NTR system. Six MTZ analogs were found, and the cell-ablation ability of these analogs was tested in zebrafish larvae. The results revealed that two of the NTR substrates, Furazolidone and Ronidazole, ablated target cells more efficiently than MTZ at lower concentrations. Furthermore, the working concentration of Ronidazole, but not Furazolidone and MTZ, did not affect axonal bridge formation during spinal cord regeneration. Our results, taken together, indicate that Ronidazole is a superior prodrug to MTZ for the NTR system, especially for the study of neuron regeneration in zebrafish larvae.
- MTZ,
- Ronidazole,
- NTR,
- Cell ablation,
- Regeneration,
- Zebrafish

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References(49)

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