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The ‘definitive’ (and ‘primitive’) guide to zebrafish hematopoiesis
Abstract
Progressive advances using zebrafish as a model organism have provided hematologists with an additional genetic system to study blood cell formation and hematological malignancies. Despite extensive evolutionary divergence between bony fish (teleosts) and mammals, the molecular pathways governing hematopoiesis have been highly conserved. As a result, most (if not all) of the critical hematopoietic transcription factor genes identified in mammals have orthologues in zebrafish. As in other vertebrates, all of the teleost blood lineages are believed to originate from a pool of pluripotent, self-renewing hematopoietic stem cells. Here, we provide a detailed review of the timing, anatomical location, and transcriptional regulation of zebrafish 'primitive' and 'definitive' hematopoiesis as well as discuss a model of T-cell leukemia and recent advances in blood cell transplantation. Given that many of the regulatory genes that control embryonic hematopoiesis have been implicated in oncogenic pathways in adults, an understanding of blood cell ontogeny is likely to provide insights into the pathophysiology of human leukemias.
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“Hematopoiesis in zebrafish embryos occurs in three distinct waves: primitive, transient, and definitive (Davidson & Zon, 2004).”
From Deciphering the toxic effects of polystyrene nanoparticles on erythropoiesis at single-cell resolution (2025) · cites this paper as Davidson & Zon, 2004
In the citing paper
“The primitive wave initiates the generation of blood cells to supply oxygen and establish the immune system (Davidson & Zon, 2004; Kulkeaw & Sugiyama, 2012).”
From Deciphering the toxic effects of polystyrene nanoparticles on erythropoiesis at single-cell resolution (2025) · cites this paper as Davidson & Zon, 2004
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Expression of LIM-domain binding protein (ldb) genes during zebrafish embryogenesis
Toyama, R., Kobayashi, M., Tomita, T., & Dawid, I. B. (1998) · Mechanisms of Development · doi:10.1016/s0925-4773(97)00202-5 · Cited by 32
Self-renewal of the long-term repopulating stem cell.
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Melanoma development and pigment cell transformation in xiphophorus
Wellbrock, C., Gómez, A., & Schartl, M. (2002) · Microscopy Research and Technique · doi:10.1002/jemt.10163 · Cited by 30
Haemopoietic centres in the developing angelfish,Pterophyllum scalare (cuvier and valenciennes)
Al-Adhami, M. A., & Kunz, Y. W. (1976) · Development Genes and Evolution · doi:10.1007/bf00848245 · Cited by 30
PU.1 supports proliferation of immature erythroid progenitors
Fisher, R. C., Slayton, W. B., Chien, C. D., Guthrie, S. M., Bray, C. L., & Scott, E. W. (2003) · Leukemia Research · doi:10.1016/s0145-2126(03)00178-4 · Cited by 29
Idiopathic Premacular Gliosis in Children and Adolescents
Kimmel, A. S., Weingeist, T. A., Blodi, C. F., & Wells, K. K. (1989) · American Journal of Ophthalmology · doi:10.1016/0002-9394(89)90437-6 · Cited by 26
Isolation and characterization of zebrafish NFE2
Pratt, S. J. P., Drejer, A. H., Foott, H., Barut, B., Brownlie, A., Postlethwait, J. H., Kato, Y., Yamamoto, M. P., & Zon, L. I. (2002) · Physiological Genomics · doi:10.1152/physiolgenomics.00112.2001 · Cited by 23
Self-citationLesser Known Aquarium Fish Tumor Models
Slatick, M. S., & Harshbarger, J. C. (2001) · Marine Biotechnology · doi:10.1007/s10126-001-0033-2 · Cited by 18
Schwarzenberger, P. O., Kolls, J. K., & Russa, V. L. (2002) · Cancer Investigation · doi:10.1081/cnv-120000373 · Cited by 11
Flagged first, then by citations
Research works printed but not linked: 6
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- Ransom DG, Bahary N, Niss K, Traver D, Burns C, Paffett-Lugassy N, Saganic WJ, Lim CA, Hersey C, Zhou Y, Barut BA, Lin S, Kingsley PD, Palis J, Orkin SH and Zon LI . (2004). PloS. Biol., in press.
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Cited by
Sorted by citations
The zebrafish lysozyme C promoter drives myeloid-specific expression in transgenic fish
Hall, C. J., Flores, M. V., Storm, T., Crosier, K., & Crosier, P. S. (2007) · BMC Developmental Biology · doi:10.1186/1471-213x-7-42 · Cited by 589
Murayama, E., Kissa, K., Zapata, A. G., Mordelet, E., Briolat, V., Lin, H.-F., Handin, R. I., & Herbomel, P. (2006) · Immunity · doi:10.1016/j.immuni.2006.10.015 · Cited by 545
Molecular Genetics of Axis Formation in Zebrafish
Schier, A. F., & Talbot, W. S. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.37.110801.143752 · Cited by 499
Zebrafish: Model for the Study of Inflammation and the Innate Immune Response to Infectious Diseases
Novoa, B., & Figueras, A. J. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0106-3_15 · Cited by 297
Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface
Hunter, M. V., Moncada, R. M., Weiss, J. M., Yanai, I., & White, R. M. (2021) · Nature Communications · doi:10.1038/s41467-021-26614-z · Cited by 295
Metadata
- Authors
- Davidson, A. J., & Zon, L. I.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Zon, Leonard I
- Venue
- Oncogene
- Published
- 2004-09-20
- Volume
- 23
- Issue
- 43
- Pages
- 7233-7246
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2032417286
- Cited by
- 419
- References
- 108
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 19 · 2023: 12 · 2022: 21 · 2021: 18 · 2020: 18 · 2019: 20 · 2018: 25 · 2017: 24 · 2016: 26 · 2015: 16 · 2014: 25 · 2013: 17 · 2012: 21
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- definitive hematopoiesis, primitive hematopoiesis, hematopoietic stem cells, hematopoietic transcription factors, orthologs, T-cell leukemia, hematologic malignancies, leukemogenesis
- MeSH terms
- Animals, Blood Cells, Embryo, Nonmammalian, Forecasting, Gastrula, Genetic Complementation Test, Growth Substances, Hematopoiesis, Hematopoietic Stem Cells, Leukemia, Mesoderm, Radiation Chimera, Transcription Factors, Transcription, Genetic, Zebrafish, Mutagenesis, Hematopoietic Stem Cell Transplantation, Gene Expression Regulation, Developmental, Cell Lineage, Models, Animal, Zebrafish Proteins, Animals, Genetically Modified, Pluripotent Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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