Hematopoiesis is a precisely orchestrated process regulated by the activity of hematopoietic cytokines and their respective receptors. Due to an extra round of whole genome duplication during vertebrate evolution in teleost fish, zebrafish have two paralogs of many important genes, including genes involved in hematopoiesis. Importantly, these duplication events brought increased level of complexity in such cases, where both ligands and receptors have been duplicated in parallel. Therefore, precise understanding of binding specificities between duplicated ligand-receptor signalosomes as well as understanding of their differential expression provide an important basis for future studies to better understand the role of duplication of these genes. However, although many recent studies in the field have partly addressed functional redundancy or sub-specialization of some of those duplicated paralogs, this information remains to be scattered over many publications and unpublished data. Therefore, the focus of this review is to provide an overview of recent findings in the zebrafish hematopoietic field regarding activity, role and specificity of some of the hematopoietic cytokines with emphasis on crucial regulators of the erythro-myeloid lineages.

Department of Cell Differentiation Institute of Molecular Genetics of the ASCR v v i Prague Czechia

Department of Cellular and Molecular Medicine University of California San Diego La Jolla CA United States

Zobrazit více v PubMed

Abbaspour Babaei M., Kamalidehghan B., Saleem M., Huri H. Z., Ahmadipour F. (2016). Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. PubMed DOI PMC

Akashi K., Traver D., Miyamoto T., Weissman I. L. (2000). A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. PubMed DOI

Alexander W. S. (1999a). Thrombopoietin and the c-Mpl receptor: insights from gene targeting. PubMed

Alexander W. S. (1999b). Thrombopoietin. PubMed DOI

Amores A., Catchen J., Ferrara A., Fontenot Q., Postlethwait J. H. (2011). Genome evolution and meiotic maps by massively parallel DNA sequencing: spotted gar, an outgroup for the teleost genome duplication. PubMed DOI PMC

Ashman L. K. (1999). The biology of stem cell factor and its receptor C-kit. PubMed DOI

Avery S., Rothwell L., Degen W. D., Schijns V. E., Young J., Kaufman J., et al. (2004). Characterization of the first nonmammalian T2 cytokine gene cluster: the cluster contains functional single-copy genes for IL-3, IL-4, IL-13, and GM-CSF, a gene for IL-5 that appears to be a pseudogene, and a gene encoding another cytokinelike transcript, KK34. PubMed DOI

Bartunek P., Pajer P., Karafiat V., Blendinger G., Dvorak M. (2002). bFGF signaling and v-Myb cooperate in sustained growth of primitive erythroid progenitors. PubMed DOI

Braasch I., Salzburger W., Meyer A. (2006). Asymmetric evolution in two fish-specifically duplicated receptor tyrosine kinase paralogons involved in teleost coloration. PubMed DOI

Broudy V. C. (1997). Stem cell factor and hematopoiesis. PubMed

Butko E., Distel M., Pouget C., Weijts B., Kobayashi I., Ng K., et al. (2015). Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo. PubMed DOI PMC

Constantinescu S. N., Ghaffari S., Lodish H. F. (1999). The Erythropoietin receptor: structure. activation and intracellular signal transduction. PubMed DOI

de Sauvage F. J., Hass P. E., Spencer S. D., Malloy B. E., Gurney A. L., Spencer S. A., et al. (1994). Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. PubMed DOI

Drachman J. G., Kaushansky K. (1997). Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain. PubMed DOI PMC

Force A., Lynch M., Pickett F. B., Amores A., Yan Y. L., Postlethwait J. (1999). Preservation of duplicate genes by complementary, degenerative mutations. PubMed PMC

Fuchs O., Simakova O., Klener P., Cmejlova J., Zivny J., Zavadil J., et al. (2002). Inhibition of Smad5 in human hematopoietic progenitors blocks erythroid differentiation induced by BMP4. PubMed DOI

Gandrillon O., Schmidt U., Beug H., Samarut J. (1999). TGF-beta cooperates with TGF-alpha to induce the self-renewal of normal erythrocytic progenitors: evidence for an autocrine mechanism. PubMed DOI PMC

Ginhoux F., Greter M., Leboeuf M., Nandi S., See P., Gokhan S., et al. (2010). Fate mapping analysis reveals that adult microglia derive from primitive macrophages. PubMed DOI PMC

Gordon M. S., Hoffman R. (1992). Growth factors affecting human thrombocytopoiesis: potential agents for the treatment of thrombocytopenia. PubMed

Greter M., Lelios I., Pelczar P., Hoeffel G., Price J., Leboeuf M., et al. (2012). Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia. PubMed DOI PMC

Guermonprez P., Helft J., Claser C., Deroubaix S., Karanje H., Gazumyan A., et al. (2013). Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection. PubMed DOI PMC

Hamilton J. A. (2008). Colony-stimulating factors in inflammation and autoimmunity. PubMed DOI

Hamilton J. A., Achuthan A. (2013). Colony stimulating factors and myeloid cell biology in health and disease. PubMed DOI

Harandi O. F., Hedge S., Wu D. C., McKeone D., Paulson R. F. (2010). Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors. PubMed DOI PMC

Hayman M. J., Meyer S., Martin F., Steinlein P., Beug H. (1993). Self-renewal and differentiation of normal avian erythroid progenitor cells: regulatory roles of the TGF alpha/c-ErbB and SCF/c-kit receptors. PubMed DOI

He B. L., Shi X., Man C. H., Ma A. C., Ekker S. C., Chow H. C., et al. (2014). Functions of flt3 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. PubMed DOI PMC

Heinrich P. C., Behrmann I., Haan S., Hermanns H. M., Muller-Newen G., Schaper F. (2003). Principles of interleukin (IL)-6-type cytokine signalling and its regulation. PubMed DOI PMC

Herbomel P., Thisse B., Thisse C. (1999). Ontogeny and behaviour of early macrophages in the zebrafish embryo. PubMed

Hoegg S., Brinkmann H., Taylor J. S., Meyer A. (2004). Phylogenetic timing of the fish-specific genome duplication correlates with the diversification of teleost fish. PubMed DOI

Huang T., Cui J., Li L., Hitchcock P. F., Li Y. (2012). The role of microglia in the neurogenesis of zebrafish retina. PubMed DOI PMC

Huber T. L., Zhou Y., Mead P. E., Zon L. I. (1998). Cooperative effects of growth factors involved in the induction of hematopoietic mesoderm. PubMed

Huising M. O., Kruiswijk C. P., Flik G. (2006). Phylogeny and evolution of class-I helical cytokines. PubMed DOI

Huising M. O., Kruiswijk C. P., van Schijndel J. E., Savelkoul H. F., Flik G., Verburg-van Kemenade B. M. (2005). Multiple and highly divergent IL-11 genes in teleost fish. PubMed DOI

Hultman K. A., Bahary N., Zon L. I., Johnson S. L. (2007). Gene Duplication of the zebrafish kit ligand and partitioning of melanocyte development functions to kit ligand a. PubMed DOI PMC

Jacobsen R. N., Nowlan B., Brunck M. E., Barbier V., Winkler I. G., Levesque J. P. (2016). Fms-like tyrosine kinase 3 (Flt3) ligand depletes erythroid island macrophages and blocks medullar erythropoiesis in the mouse. PubMed DOI

Kato T., Matsumoto A., Ogami K., Tahara T., Morita H., Miyazaki H. (1998). Native thrombopoietin: structure and function. PubMed DOI

Kaushansky K. (2006). Lineage-specific hematopoietic growth factors. PubMed DOI

Kaushansky K., Broudy V. C., Grossmann A., Humes J., Lin N., Ren H. P., et al. (1995). Thrombopoietin expands erythroid progenitors, increases red cell production, and enhances erythroid recovery after myelosuppressive therapy. PubMed DOI PMC

Kosmider O., Denis N., Lacout C., Vainchenker W., Dubreuil P., Moreau-Gachelin F. (2005). Kit-activating mutations cooperate with Spi-1/PU.1 overexpression to promote tumorigenic progression during erythroleukemia in mice. PubMed DOI

Krantz S. B. (1991). Erythropoietin. PubMed

Krystal G. (1994). Transforming growth factor beta 1 is an inducer of erythroid differentiation. PubMed DOI PMC

Lieschke G. J., Grail D., Hodgson G., Metcalf D., Stanley E., Cheers C., et al. (1994). Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. PubMed

Liongue C., Ward A. C. (2007). Evolution of Class I cytokine receptors. PubMed DOI PMC

Liu F., Wu H. Y., Wesselschmidt R., Kornaga T., Link D. C. (1996). Impaired production and increased apoptosis of neutrophils in granulocyte colony-stimulating factor receptor-deficient mice. PubMed DOI

Macaulay I. C., Svensson V., Labalette C., Ferreira L., Hamey F., Voet T., et al. (2016). Single-Cell RNA-Sequencing reveals a continuous spectrum of differentiation in hematopoietic cells. PubMed DOI PMC

Mahony C. B., Fish R. J., Pasche C., Bertrand J. Y. (2016). tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis. PubMed DOI

Mahony C. B., Pasche C., Bertrand J. Y. (2018). Oncostatin M and kit-ligand control hematopoietic stem cell fate during zebrafish embryogenesis. PubMed DOI PMC

Martinez F. O., Gordon S. (2014). The M1 and M2 paradigm of macrophage activation: time for reassessment. PubMed DOI PMC

McNiece I. K., Langley K. E., Zsebo K. M. (1991). Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and epo to stimulate human progenitor cells of the myeloid and erythroid lineages. PubMed

Mellgren E. M., Johnson S. L. (2005). kitb, a second zebrafish ortholog of mouse Kit. PubMed DOI

Metcalf D. (1985). The granulocyte-macrophage colony-stimulating factors. PubMed DOI

Metcalf D., Nicola N. A. (1983). Proliferative effects of purified granulocyte colony-stimulating factor (G-CSF) on normal mouse hemopoietic cells. PubMed DOI

Migliaccio G., Migliaccio A. R., Adamson J. W. (1988). In vitro differentiation of human granulocyte/macrophage and erythroid progenitors: comparative analysis of the influence of recombinant human erythropoietin, G-CSF, GM-CSF, and IL-3 in serum-supplemented and serum-deprived cultures. PubMed

Migliaccio G., Migliaccio A. R., Adamson J. W. (1991). In vitro differentiation and proliferation of human hematopoietic progenitors: the effects of interleukins 1 and 6 are indirectly mediated by production of granulocyte-macrophage colony-stimulating factor and interleukin 3. PubMed

Miyagawa S., Kobayashi M., Konishi N., Sato T., Ueda K. (2000). Insulin and insulin-like growth factor I support the proliferation of erythroid progenitor cells in bone marrow through the sharing of receptors. PubMed DOI

Muir A. R., Kerr D. N. (1958). Erythropoiesis: an electron microscopical study. PubMed DOI

Nei M., Roychoudhury A. K. (1973). Probability of fixation and mean fixation time of an overdominant mutation. PubMed PMC

Nicola N. A. (1994). Cytokine pleiotropy and redundancy: a view from the receptor. PubMed

Nicola N. A., Begley C. G., Metcalf D. (1985). Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells. PubMed DOI

Nicola N. A., Metcalf D., Matsumoto M., Johnson G. R. (1983). Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. PubMed

Paffett-Lugassy N., Hsia N., Fraenkel P. G., Paw B., Leshinsky I., Barut B., et al. (2007). Functional conservation of erythropoietin signaling in zebrafish. PubMed DOI PMC

Pagan A. J., Yang C. T., Cameron J., Swaim L. E., Ellett F., Lieschke G. J., et al. (2015). Myeloid growth factors promote resistance to mycobacterial infection by curtailing Granuloma necrosis through macrophage replenishment. PubMed DOI PMC

Parichy D. M., Rawls J. F., Pratt S. J., Whitfield T. T., Johnson S. L. (1999). Zebrafish sparse corresponds to an orthologue of c-kit and is required for the morphogenesis of a subpopulation of melanocytes, but is not essential for hematopoiesis or primordial germ cell development. PubMed

Patterson L. B., Bain E. J., Parichy D. M. (2014). Pigment cell interactions and differential xanthophore recruitment underlying zebrafish stripe reiteration and Danio pattern evolution. PubMed DOI PMC

Paul S. R., Bennett F., Calvetti J. A., Kelleher K., Wood C. R., O’Hara R. M., et al. (1990). Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. PubMed DOI PMC

Pixley F. J., Stanley E. R. (2004). CSF-1 regulation of the wandering macrophage: complexity in action. PubMed DOI

Ratnoff O. D. (1987). The evolution of hemostatic mechanisms. PubMed DOI

Schneider W., Gattermann N. (1994). Megakaryocytes: origin of bleeding and thrombotic disorders. PubMed DOI

Simpson C. F. (1967). The mechanism of denucleation in circulating erythroblasts. PubMed DOI PMC

Stachura D. L., Reyes J. R., Bartunek P., Paw B. H., Zon L. I., Traver D. (2009). Zebrafish kidney stromal cell lines support multilineage hematopoiesis. PubMed DOI PMC

Stachura D. L., Svoboda O., Campbell C. A., Espin-Palazon R., Lau R. P., Zon L. I., et al. (2013). The zebrafish granulocyte colony-stimulating factors (Gcsfs): 2 paralogous cytokines and their roles in hematopoietic development and maintenance. PubMed DOI PMC

Stachura D. L., Svoboda O., Lau R. P., Balla K. M., Zon L. I., Bartunek P., et al. (2011). Clonal analysis of hematopoietic progenitor cells in the zebrafish. PubMed DOI PMC

Steinlein P., Wessely O., Meyer S., Deiner E. M., Hayman M. J., Beug H. (1995). Primary, self-renewing erythroid progenitors develop through activation of both tyrosine kinase and steroid hormone receptors. PubMed DOI

Svoboda O., Bartunek P. (2015). Origins of the vertebrate erythro/megakaryocytic system. PubMed DOI PMC

Svoboda O., Stachura D. L., Machonova O., Pajer P., Brynda J., Zon L. I., et al. (2014). Dissection of vertebrate hematopoiesis using zebrafish thrombopoietin. PubMed DOI PMC

Takahata N., Maruyama T. (1979). Polymorphism and loss of duplicate gene expression: a theoretical study with application of tetraploid fish. PubMed DOI PMC

Tan Y. Y., Kodzius R., Tay B. H., Tay A., Brenner S., Venkatesh B. (2012). Sequencing and analysis of full-length cDNAs, 5′-ESTs and 3′-ESTs from a cartilaginous fish, the elephant shark ( PubMed DOI PMC

Tang Q., Iyer S., Lobbardi R., Moore J. C., Chen H., Lareau C., et al. (2017). Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing. PubMed DOI PMC

Tornack J., Kawano Y., Garbi N., Hammerling G. J., Melchers F., Tsuneto M. (2017). Flt3 ligand-eGFP-reporter expression characterizes functionally distinct subpopulations of CD150(+) long-term repopulating murine hematopoietic stem cells. PubMed DOI

Touw I. P., van de Geijn G. J. (2007). Granulocyte colony-stimulating factor and its receptor in normal myeloid cell development, leukemia and related blood cell disorders. PubMed DOI

van Ham T. J., Oosterhof N., Kuil L. E., van der Linde H. C., Geurts S. N., Meijering E. (2018). Reverse genetic screen reveals that Il34 facilitates yolk sac macrophage distribution and seeding of the brain. PubMed DOI PMC

Wang T., Hanington P. C., Belosevic M., Secombes C. J. (2008). Two macrophage colony-stimulating factor genes exist in fish that differ in gene organization and are differentially expressed. PubMed DOI

Wang Y., Szretter K. J., Vermi W., Gilfillan S., Rossini C., Cella M., et al. (2012). IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. PubMed DOI PMC

Watterson G. A. (1983). On the time for gene silencing at duplicate Loci. PubMed PMC

Wu S., Xue R., Hassan S., Nguyen T. M. L., Wang T., Pan H., et al. (2018). Il34-Csf1r pathway regulates the migration and colonization of microglial precursors. PubMed DOI

M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands