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Normal Hemopoiesis

The role of survivin2 in primitive hematopoiesis during zebrafish development

Leukemia volume 23, pages 712–720 (2009)Cite this article

Abstract

Survivin is an inhibitor of apoptosis and its role in embryonic development is not completely understood. In zebrafish, survivin undergoes gene duplication. Survivin1 (sur1) has been shown to mediate angiogenesis but not hematopoiesis. In this study, we examined survivin2 (sur2) with particular reference to its role in primitive hematopoiesis during zebrafish development. sur2 was expressed predominantly in the intermediate cell mass (ICM, site of primitive hematopoiesis). Morpholino (MO) targeting at intron1–exon2 junction of sur2 significantly reduced green fluorescent protein+ (erythroid) cell population in transgenic Tg (gata1:gfp) embryos at 18 h post-fertilization (h.p.f.; wild type: 4.49±0.15%; Sur2MO embryos: 2.22±0.12%, P=0.02). Molecular targeting was confirmed by reverse transcription–PCR and MO specificity by successful sur2 mRNA rescue. sur2 MO also downregulated genes associated with hematopoietic stem cells (scl, lmo2), erythroid (gata1, α- and β-embryonic hemoglobins) as well as early (pu.1) and late (mpo, l-plastin) myelomonocytic lineages at 12 and 18 h.p.f. This was associated with an increase in apoptosis in the ICM and alteration of cell-cycle status of erythroid cells. Both effects were caspase dependent. In conclusion, sur2 is important in maintaining hematopoietic stem and lineage committed cells during zebrafish development, by virtue of its antiapoptotic activity in a caspase dependent and cell autonomous fashion.

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Acknowledgements

We thank Jessie Fu and Babs Kwok for performing some of the microinjection experiments and to Mr Howard Chow for part of the molecular studies. We also thank Dr Anming Meng (Tsinghua University, China) for the generous gift of the Tg(gata1:gfp) fish lines. We also thank the live cell imaging core facility of the Department of Anatomy for the confocal microscopy. This work was supported by the Competitive Earmarked Research Grants (CERG; HKU 7520/06M, HKU 7488/04M, HKU 7538/05M) and an internal research grant from HKU.

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  1. Division of Haematology and Bone Marrow Transplantation, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China

    A C H Ma, M I S Chung, R Liang & A Y H Leung

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  1. A C H Ma
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  2. M I S Chung
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  3. R Liang
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  4. A Y H Leung
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Correspondence to A Y H Leung.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Ma, A., Chung, M., Liang, R. et al. The role of survivin2 in primitive hematopoiesis during zebrafish development. Leukemia 23, 712–720 (2009). https://doi.org/10.1038/leu.2008.363

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