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Opposite effects of FGF and BMP-4 on embryonic blood formation: Roles of PV.1 and GATA-2

  1. Author:
    Xu, R. H.
    Ault, K. T.
    Kim, J.
    Park, M. J.
    Hwang, Y. S.
    Peng, Y.
    Sredni, D.
    Kung, H. F.

  2. Author Address

    Kung HF NCI, Lab Biochem Physiol, Div Basic Sci Frederick, MD 21702 USA NCI, Lab Biochem Physiol, Div Basic Sci Frederick, MD 21702 USA NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr Frederick, MD 21702 USA NICHHD, Genet Mol Lab, NIH Bethesda, MD 20892 USA Hallym Univ, Coll Med, Dept Biochem Chun Cheon South Korea Kyungpook Natl Univ, Sch Med, Dept Anat Taegu 700422 South Korea Bar Ilan Univ, Interdisciplinary Dept IL-52900 Ramat Gan Israel Univ Hong Kong, Inst Mol Biol Hong Kong Hong Kong
    1. Year: 1999
  2. Journal: Developmental Biology
    1. 208
    2. 2
    3. Pages: 352-361
  4. Type of Article: Article
  1. Abstract:

    In adult vertebrates, fibroblast growth factor (FGF) synergizes with many hematopoietic cytokines to stimulate the proliferation of hematopoietic progenitors. In vertebrate development, the FGF signaling pathway is important in the formation of some derivatives of ventroposterior mesoderm. However, the function of FGF in the specification of the embryonic erythropoietic lineage has remained unclear. Here we address the role of FGF in the specification of the erythropoietic lineage in the Xenopus embryo. We report that ventral injection of embryonic FGF (eFGF) mRNA at as little as 10 pg at the four-cell stage suppresses ventral blood island (VBI) formation, whereas expression of the dominant negative form of the EGF receptor in the lateral mesoderm, where physiologically no blood tissue is formed, results in a dramatic expansion of the VBI. Similar results were observed in isolated ventral marginal zones and animal caps. Bone morphogenetic protein-4 (BMP-4) is known to induce erythropoiesis in the Xenopus embryo. Therefore, we examined how the BMP-4 and EGF signaling pathways might interact in the decision of ventral mesoderm to form blood. We observed that eFGF inhibits BMP-4-induced erythropoiesis by differentially regulating expression of the BMP-4 downstream effecters GATA-2 and PV.1. GATA-2 which stimulates erythropoiesis, is suppressed by FGF. PV.1, which we demonstrate to inhibit blood development, is enhanced by FGF. Additionally, PV.1 and GATA-2 negatively regulate transcription of each other. Thus, BMP-4 induces two transcription factors which have opposing effects on blood development. The EGF and BMP-4 signaling pathways interact to regulate the specification of the erythropoietic lineage. (C) 1999 Academic Press. [References: 54]

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