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

Ren He Xu, Katherine Tidman Ault, Jaebong Kim, Mae Ja Park, Yoo Seok Hwang, Ying Peng, Dvora Sredni, Hsiang Fu Kung

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46 Scopus citations


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 FGF 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 FGF 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 effectors 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 FGF and BMP-4 signaling pathways interact to regulate the specification of the erythropoietic lineage.

Original languageEnglish
Pages (from-to)352-361
Number of pages10
JournalDevelopmental Biology
Issue number2
StatePublished - 15 Apr 1999

Bibliographical note

Funding Information:
H. V. Isaacs for the pSP64T-eFGF and CSKA-eFGF, and Mrs. Annie Rogers for editing the manuscript. This work was supported with federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-56000 and by the Shiff-man Program for Clinical and Basic Research between Bar Ilan University of Israel and the National Cancer Institute of the United States. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Funding Information:
We thank Dr. Igor Dawid and the National Institute of Child Health and Human Development for financial support for part of this project and Dr. Igor Dawid for critically reading the manuscript. We also appreciate Dr. E. Amaya for the pSP64T-XFD, Dr.


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