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Updated: Sep 9, 2026
Mechanical Vessel Injury in Zebrafish Embryos
Published on: February 17, 2015
An inducible zebrafish model of thrombocytopenia enables in vivo drug screening and reveals fibroblast growth factor
Jialong Deng1, Jiajun Chen2, Yuanbing Wang2
1Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, China; Department of Hematology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China.
Background:
Thrombocytopenia is a serious hematological disorder characterized by low platelet counts, with platelet recovery rate as a key prognostic factor. Current models have limitations, including acute toxicity, nonspecific cell ablation, and limited capacity to observe dynamic recovery.
Objectives:
This study aimed to establish a thrombocyte-specific ablation zebrafish model to study thrombocyte regeneration and screen for prorecovery compounds.
Methods:
We generated a Tg(cd41:enhanced green fluorescent protein [eGFP]-nitroreductase [NTR]) zebrafish model to induce thrombocyte ablation using ronidazole. The model was characterized by imaging, phenotypic assays, and transcriptomics. A targeted library of 132 compounds was screened, and hits were validated in the chemotherapy-induced thrombocytopenia and congenital amegakaryocytic thrombocytopenia zebrafish models, as well as in human Meg-01 cells.
Results:
Ronidazole treatment caused rapid, specific thrombocyte depletion through cell-autonomous apoptosis and macrophage-mediated clearance. This loss led to bleeding symptoms and reduced thrombus formation, resembling key features of thrombocytopenia. Transcriptomic analysis and functional studies showed that fibroblast growth factor signaling plays a critical role in thrombocyte recovery. Screening of the compound library identified 3 novel candidates that significantly accelerated recovery. Notably, tasisulam effectively rescued both chemotherapy-induced thrombocytopenia and congenital amegakaryocytic thrombocytopenia phenotypes by driving thrombocyte recovery via the extracellular signal-regulated kinase signaling pathway. In addition, both tasisulam and 4-methylcatechol promoted thrombopoiesis in human Meg-01 cells, indicating conservation across species.
Conclusion:
The Tg(cd41:eGFP-NTR) zebrafish model provides exceptional spatiotemporal resolution for investigating the pathogenesis and in vivo recovery dynamics of thrombocytopenia. It serves as a versatile platform for identifying therapeutic agents with cross-species efficacy and uncovering key mechanisms that regulate thrombocyte regeneration, revealing fibroblast growth factor signaling as a central regulator of thrombocyte recovery.
